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1.
Braz J Med Biol Res ; 52(11): e8657, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31664305

RESUMO

Although Taxol has improved the survival of cancer patients as a first-line chemotherapeutic agent, an increasing number of patients develop resistance to Taxol after prolonged treatment. The potential mechanisms of cancer cell resistance to Taxol are not completely clear. It has been reported that microRNAs (miRNAs) are involved in regulating the sensitivity of cancer cells to various chemotherapeutic agents. In this study, we aimed to explore the role of miR-129-5p in regulating the sensitivity of breast cancer cells to Taxol. Cell apoptosis and autophagy, and the sensitivity of MCF-7 cells to Taxol were assessed with a series of in vitro assays. Our results showed that the inhibition of autophagy increased the Taxol-induced apoptosis and the sensitivity of MCF-7 cells to Taxol. Up-regulation of miR-129-5p also inhibited autophagy and induced apoptosis. Furthermore, miR-129-5p overexpression increased the sensitivity of MCF-7 cells to Taxol. High mobility group box 1 (HMGB1), a target gene of miR-129-5p and a regulator of autophagy, was negatively regulated by miR-129-5p. We found that interference of HMGB1 enhanced the chemosensitivity of Taxol by inhibiting autophagy and inducing apoptosis in MCF-7 cells. Taken together, our findings suggested that miR-129-5p increased the chemosensitivity of MCF-7 cells to Taxol through suppressing autophagy and enhancing apoptosis by inhibiting HMGB1. Using miR-129-5p/HMGB1/autophagy-based therapeutic strategies may be a potential treatment for overcoming Taxol resistance in breast cancer.


Assuntos
Antineoplásicos Fitogênicos/metabolismo , Neoplasias da Mama/metabolismo , Proteína HMGB1/metabolismo , Células MCF-7/metabolismo , MicroRNAs/metabolismo , Paclitaxel/metabolismo , Antineoplásicos Fitogênicos/uso terapêutico , Apoptose/genética , Autofagia/genética , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Proteína HMGB1/genética , Humanos , MicroRNAs/genética , Paclitaxel/uso terapêutico , Regulação para Cima/genética
2.
Zhonghua Fu Chan Ke Za Zhi ; 54(9): 588-594, 2019 Sep 25.
Artigo em Chinês | MEDLINE | ID: mdl-31550774

RESUMO

Objective: To investigate the efficacy and side effect of paclitaxel liposome for neoadjuvant chemotherapy (NACT) in locally advanced cervical cancer. Methods: This study were included 265 cervical cancer patients staging Ⅰb2 and Ⅱa2 who underwent paclitaxel-platinum NACT followed by radical surgery from June 2008 to December 2016 in the Cancer Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences. All patients were classified into two groups with 106 patients in paclitaxel liposome group and 159 patients in traditional paclitaxel group. The difference in clinicopathologic characteristics, efficacy and side effect were analyzed retrospectively between the two groups. Results: (1) Clinicopathologic characteristics: there were no significant difference in clinicopathologic characteristics between the two groups, including age, body mass index, clinical stage, pathological histology, cycles of NACT, combined platinum regimen, lymph-vascular space invasion, lymph node metastasis, deep stromal invasion, and postoperative adjuvant therapy (all P>0.05). (2) Efficacy: after NACT, the overall response occurred in 90 (15 complete response plus 75 partial response) of 106 cases in the paclitaxel liposome group versus 131 (21 complete response plus 110 partial response) of 159 cases in the traditional paclitaxel group without statistical significance (84.9% vs 82.4%; χ(2)=0.291, P=0.590). A total of 248 patients received surgery after NACT and were evaluable in survival. The 5-year recurrence-free survival (RFS) rate and 5-year overall survival (OS) rate of these patients was 85.1% and 88.2%. The 5-year RFS rate in the paclitaxel liposome group was 85.9% compared with 85.2% in the traditional paclitaxel group, while the corresponding 5-year OS rate was 88.5% and 88.7%, respectively. There was no statistically significant difference in efficacy between the two groups (P=0.968, P=0.797). (3) Side effect: the incidence of allergic reaction between the paclitaxel liposome group and the traditional paclitaxel group was 0 versus 1.9% (3/159) without statistical significance (P=0.277). But the incidence of neurotoxicity in the paclitaxel liposome group significantly decreased compared with the traditional paclitaxel group (6.6% vs 15.7%, P<0.05), as well as the incidence of alopecia (67.9% vs 79.2%, P<0.05) and myalgia (17.9% vs 28.9%, P<0.05). However, significant differences were not found in terms of hematological toxicity, gastrointestinal reaction, and hepatic function damage (P>0.05). Conclusion: In paclitaxel-platinum NACT of local advanced cervical cancer, paclitaxel liposome can achieve similar efficacy compared with traditional paclitaxel, but paclitaxel liposome is helpful in decreasing the toxicity of neurotoxicity, alopecia and myalgia.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Quimioterapia Adjuvante/efeitos adversos , Terapia Neoadjuvante/efeitos adversos , Paclitaxel/administração & dosagem , Neoplasias do Colo do Útero/tratamento farmacológico , Quimioterapia Adjuvante/métodos , Feminino , Humanos , Lipossomos , Terapia Neoadjuvante/métodos , Estadiamento de Neoplasias , Paclitaxel/efeitos adversos , Paclitaxel/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento
3.
Cochrane Database Syst Rev ; 9: CD004421, 2019 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-31476253

RESUMO

BACKGROUND: Adjuvant chemotherapy improves survival in premenopausal and postmenopausal women with early breast cancer. Taxanes are highly active chemotherapy agents used in metastatic breast cancer. Review authors examined their role in early breast cancer. This review is an update of a Cochrane Review first published in 2007. OBJECTIVES: To assess the effects of taxane-containing adjuvant chemotherapy regimens for treatment of women with operable early breast cancer. SEARCH METHODS: For this review update, we searched the Specialised Register of the Cochrane Breast Cancer Group, MEDLINE, Embase, CENTRAL (2018, Issue 6), the WHO International Clinical Trials Registry Platform (ICTRP), and ClinicalTrials.gov on 16 July 2018, using key words such as 'early breast cancer' and 'taxanes'. We screened reference lists of other related literature reviews and articles, contacted trial authors, and applied no language restrictions. SELECTION CRITERIA: Randomised trials comparing taxane-containing regimens versus non-taxane-containing regimens in women with operable breast cancer were included. Studies of women receiving neoadjuvant chemotherapy were excluded. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed risk of bias and quality of the evidence using the GRADE approach. Hazard ratios (HRs) were derived for time-to-event outcomes, and meta-analysis was performed using a fixed-effect model. The primary outcome measure was overall survival (OS); disease-free survival (DFS) was a secondary outcome measure. Toxicity was represented as odds ratios (ORs), and quality of life (QoL) data were extracted when present. MAIN RESULTS: This review included 29 studies (27 full-text publications and 2 abstracts or online theses). The updated analysis included 41,911 randomised women; the original review included 21,191 women. Taxane-containing regimens improved OS (HR 0.87, 95% confidence interval (CI) 0.83 to 0.92; high-certainty evidence; 27 studies; 39,180 women; 6501 deaths) and DFS (HR, 0.88, 95% CI 0.85 to 0.92; high-certainty evidence; 29 studies; 41,909 women; 10,271 reported events) compared to chemotherapy without a taxane. There was moderate to substantial heterogeneity across studies for OS and DFS (respectively).When a taxane-containing regimen was compared with the same regimen without a taxane, the beneficial effects of taxanes persisted for OS (HR 0.84, 95% CI 0.77 to 0.92; P < 0.001; 7 studies; 10,842 women) and for DFS (HR 0.84, 95% CI 0.78 to 0.90; P < 0.001; 7 studies; 10,842 women). When a taxane-containing regimen was compared with the same regimen with another drug or drugs that were substituted for the taxane, a beneficial effect was observed for OS and DFS with the taxane-containing regimen (OS: HR 0.80, 95% CI 0.74 to 0.86; P < 0.001; 13 studies; 16,196 women; DFS: HR 0.83, 95% CI 0.78 to 0.88; P < 0.001; 14 studies; 16,823 women). Preliminary subgroup analysis by lymph node status showed a survival benefit with taxane-containing regimens in studies of women with lymph node-positive disease only (HR 0.83, 95% CI 0.78 to 0.88; P < 0.001; 17 studies; 22,055 women) but less benefit in studies of women both with and without lymph node metastases or with no lymph node metastases. Taxane-containing regimens also improved DFS in women with lymph node-positive disease (HR 0.84, 95% CI 0.80 to 0.88; P < 0.001; 17 studies; 22,055 women), although the benefit was marginal in studies of women both with and without lymph node-positive disease (HR 0.95, 95% CI 0.88 to 1.02; 9 studies; 12,998 women) and was not apparent in studies of women with lymph node-negative disease (HR 0.99, 95% CI 0.86 to 1.14; 3 studies; 6856 women).Taxanes probably result in a small increase in risk of febrile neutropenia (odds ratio (OR) 1.55, 95% CI 0.96 to 2.49; moderate-certainty evidence; 24 studies; 33,763 women) and likely lead to a large increase in grade 3/4 neuropathy (OR 6.89, 95% CI 3.23 to 14.71; P < 0.001; moderate-certainty evidence; 22 studies; 31,033 women). Taxanes probably cause little or no difference in cardiotoxicity compared to regimens without a taxane (OR 0.87, 95% CI 0.56 to 1.33; moderate-certainty evidence; 23 studies; 32,894 women). Seven studies reported low-quality evidence for QoL; overall, taxanes may make little or no difference in QoL compared to chemotherapy without a taxane during the follow-up period; however, the duration of follow-up differed across studies. Only one study, which was conducted in Europe, provided cost-effectiveness data. AUTHORS' CONCLUSIONS: This review of studies supports the use of taxane-containing adjuvant chemotherapy regimens, with improvement in overall survival and disease-free survival for women with operable early breast cancer. This benefit persisted when analyses strictly compared a taxane-containing regimen versus the same regimen without a taxane or the same regimen with another drug that was substituted for the taxane. Preliminary evidence suggests that taxanes are more effective for women with lymph node-positive disease than for those with lymph node-negative disease. Considerable heterogeneity across studies probably reflects the varying efficacy of the chemotherapy backbones of the comparator regimens used in these studies. This review update reports results that are remarkably consistent with those of the original review, and it is highly unlikely that this review will be updated, as new trials are assessing treatments based on more detailed breast cancer biology.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama/tratamento farmacológico , Taxoides/uso terapêutico , Quimioterapia Adjuvante , Feminino , Humanos , Terapia Neoadjuvante , Paclitaxel/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto
4.
Cell Mol Biol Lett ; 24: 47, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31308851

RESUMO

Background: Chemotherapy based on paclitaxel (PTX) is the standard treatment for a range of cancers, including triple-negative breast cancer (TNBC), but the increasing development of resistance has reduced/has negatively impacted its clinical utility. A previous study demonstrated that miR-5195-3p could suppress lung cancer cell growth. This study was designed to investigate whether miR-5195-3p attenuates chemoresistance to PTX by regulating target genes in TNBC cells. Methods: The study used both PTX-resistant tumor tissues and PTX-resistant TNBC cell lines. The expression of miR-5195-3p was determined using quantitative real-time PCR. Cell viability, cell cycle distribution and apoptosis were analyzed using CCK-8 and flow cytometry assays. The target genes of miR-5195-3p were predicted with bioinformatics analysis and confirmed using the luciferase reporter assay. Results: MiR-5195-3p expression was lower in PTX-resistant tumor tissues and PTX-resistant TNBC cell lines. Upregulation of miR-5195-3p enhanced the sensitivity of PTX-resistant TNBC cells to PTX treatment. EIF4A2 was confirmed as a potential target of miR-5195-3p. EIF4A2 knockdown imitated the effects of miR-5195-3p on chemosensitivity, while restoration of EIF4A2 rescued them. Conclusion: These data demonstrate that miR-5195-3p might be a potential therapeutic target to reverse chemoresistance in TNBC through its targeting of EIF4A2.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Fator de Iniciação 4A em Eucariotos/genética , MicroRNAs/metabolismo , Paclitaxel/uso terapêutico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismo , Apoptose , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Células MCF-7 , Neoplasias de Mama Triplo Negativas/fisiopatologia
5.
BMC Complement Altern Med ; 19(1): 161, 2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31277622

RESUMO

BACKGROUND: Cervical cancer is the second most prevalent cancer worldwide. Portulaca oleracea L. polysaccharide (POL-P3b) has been found to have enhancing immune and anti-cervical cancer activity by oral administration. Dendritic cells (DC) play a key roles in regulating intestinal immune homeostasis. In this study, we analyzed the inhibition apoptosis effects of POL-P3b on intestinal DC and relevant mechanisms. METHODS: Intestinal DC was isolated from U14-bearing mice treated with POL-P3b (50 mg/kg, 100 mg/kg and 200 mg/kg, respectively). The effects of POL-P3b on proliferation and inhibiting apoptosis in intestinal DC were evaluated by MTT assay, Hoechst 33342 and Annexin V-FITC/PI staining. Mitochondrial Ca2+ was analyzed using flow cytometry instrument. The potential mechanisms underlying POL-P3b-induced protection of intestinal DC from cervical cancer-induced apoptosis were detected with Western blotting evaluation of expression levels of TLR4 and relevant proteins for apoptotic signaling pathway. RESULTS: We found that a large number of intestinal DC were apoptosis in U14-bearing mice. Treatment with POL-P3b in U14-bearing mice at different doses for 12 d resulted in a significant increase in intestinal DC survival, and the mechanisms were related to inhibiting DC apoptosis. CONCLUSION: Our results suggested that POL-P3b-induced protection against tumor-induced intestinal DC apoptosis through stimulating the TLR4-PI3K/AKT-NF-κB signaling pathway. This study enhanced understanding of the oral administration with POL-P3b exerted on anti-tumor activity and its action mechanism.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Células Dendríticas/efeitos dos fármacos , Extratos Vegetais/farmacologia , Polissacarídeos/farmacologia , Portulaca/química , Administração Oral , Animais , Antineoplásicos Fitogênicos/análise , Antineoplásicos Fitogênicos/uso terapêutico , Cálcio/metabolismo , Carcinoma/tratamento farmacológico , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Intestinos/imunologia , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Fitoterapia , Extratos Vegetais/uso terapêutico , Polissacarídeos/uso terapêutico , Transdução de Sinais , Neoplasias do Colo do Útero/tratamento farmacológico
6.
Clin Ter ; 170(4): e231-e234, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31304506

RESUMO

Primary squamous cell carcinoma of the thyroid (PSCCT) is a rare malignant disease with rapid fatal prognosis. The onset is generally characterized by sudden bilateral latero-cervical lymphadenopathy. The Authors report patient of 58-year-old who referred for evaluation of rapidly aggravating bilateral latero-cervical lymphadenopathy. The US highlighted the presence of a hypoechoic nodular lesion characterized by peri and intra-nodular vascularization. Multilayer CT showed diffused involvement of mediastinal and bilateral latero-cervical lymph nodes, with no evidence of primary pulmonary neoplasia or elsewhere. The patient underwent total thyroidectomy. The peri-isthmic tissue was removed due to the presence of a small roundish formation, that was due to lymph node metastasis at histological examination. Histological diagnosis: PSCCT. The immunohistochemical panel of the thyroid lesion was indispensable for the differential diagnosis between PSCCT, medullary carcinoma, anaplastic carcinoma, and thyroid metastasis of neoplasia with unknown primitiveness. The patient underwent chemotherapeutic treatment with Carboplatin and Paclitaxel with modest improvement of dysphagia symptoms and reduction of 10-15% of the target lesions. The clinical course was characterized by loco-regional progression of the disease with exitus in 10 months after diagnosis. Survival and quality of life after surgical therapy and chemotherapy were like that of patients undergoing only chemotherapy. Due to the extreme rarity of the neoplasia, 60 cases described in Literature, no exclusive guidelines are reported for PSCCT. More extensive case studies are needed to evaluate the effects of total thyroidectomy with intent R0/R1 on improving survival and quality of life of patients with PSCCT.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Carcinoma de Células Escamosas/cirurgia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia , Humanos , Linfadenopatia/diagnóstico , Masculino , Pessoa de Meia-Idade , Paclitaxel/uso terapêutico , Prognóstico , Qualidade de Vida , Neoplasias da Glândula Tireoide/diagnóstico
7.
Cell Mol Biol Lett ; 24: 40, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31223315

RESUMO

Paclitaxel is a well-known anticancer agent with a unique mechanism of action. It is considered to be one of the most successful natural anticancer drugs available. This study summarizes the recent advances in our understanding of the sources, the anticancer mechanism, and the biosynthetic pathway of paclitaxel. With the advancement of biotechnology, improvements in endophytic fungal strains, and the use of recombination techniques and microbial fermentation engineering, the yield of extracted paclitaxel has increased significantly. Recently, paclitaxel has been found to play a large role in tumor immunity, and it has a great potential for use in many cancer treatments.


Assuntos
Biotecnologia/métodos , Imunoterapia , Neoplasias/terapia , Paclitaxel/uso terapêutico , Animais , Antineoplásicos Fitogênicos/biossíntese , Antineoplásicos Fitogênicos/uso terapêutico , Fermentação , Fungos/metabolismo , Humanos , Neoplasias/tratamento farmacológico , Paclitaxel/biossíntese , Paclitaxel/farmacologia
8.
Chem Biol Interact ; 309: 108703, 2019 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-31194954

RESUMO

ß-2-himachalen-6-ol (HC), a major sesquiterpene isolated from the Lebanese wild carrot umbels, was shown to possess remarkable in vitro and in vivo anticancer activities. The present study investigates the anti-metastatic activity of HC post 4T1 breast cancer cells inoculation in a murine model. The effect of HC on 4T1 cell viability was assessed using WST-1 kit, while cell cycle analysis was performed using flow cytometry. Tumor development and metastasis were evaluated by injecting 4T1 cells in the mice mammary gland region followed by either HC or cisplatin treatment. The 6-thioguanine assay was used for the quantification of metastatic cells in the blood. HC treatment caused a dose-dependent decrease in cell viability with IC50 and IC90 values of 7 and 28 µg/mL respectively. Concomitant treatment with cisplatin significantly reduced cell viability when compared to cells treated with cisplatin or HC alone. Flow cytometry revealed a significant increase (p˂0.05) in cell count in the Sub-G1 phase at HC 10 µg/mL, and total DNA fragmentation (p˂0.001) at HC 25 µg/mL. Annexin/PI staining showed early and late apoptotic mode of cell death upon treatment with HC. Histopathological evaluation revealed less incidence of primary and metastatic tumor/inflammation in the HC and cisplatin treated groups. Tumor size and colony-forming units were significantly decreased in the HC treated group. HC treatment induced cell cycle arrest, promoted apoptosis and reduced the incidence of primary and metastatic lesions caused by 4T1 cells. The present findings suggest that HC has an anti-metastatic potential against aggressive types of cancer.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Sesquiterpenos/farmacologia , Animais , Antineoplásicos Fitogênicos/uso terapêutico , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Fragmentação do DNA/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , Sesquiterpenos/uso terapêutico , Pele/patologia , Transplante Homólogo , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia
9.
Environ Toxicol ; 34(8): 891-901, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31157515

RESUMO

Nepenthes plants are regarded as a kind of Traditional Chinese Medicine for several diseases but its anticancer activity remain unclear. The subject of this study is to evaluate the antiproliferation effects on oral cancer cells by Nepenthes plants using ethyl acetate extract of Nepenthes adrianii x clipeata (EANA). Cell viability was detected using MTS assay. Its detailed mechanisms including cell cycle, apoptosis, oxidative stress, and DNA damage were explored by flow cytometry or western blotting. For 24 hours EANA treatment, five kinds of oral cancer cells (CAL 27, Ca9-22, OECM-1, HSC-3, and SCC9) show IC50 values of cell viability ranging from 8 to 17 µg/mL but the viability of normal oral cells (HGF-1) remains over 80%. Subsequently, CAL 27 and Ca9-22 cells with high sensitivity to EANA were chosen to investigate the detailed mechanism. EANA displays the time course and concentration effects for inducing apoptosis based on flow cytometry (subG1 and annexin V analyses) and western blotting [cleaved poly (ADP-ribose) polymerase (c-PARP)]. Oxidative stress and DNA damage were induced by EANA treatments in oral cancer cells through reactive oxygen species (ROS), mitochondrial membrane potential disruption, mitochondrial superoxide, and γH2AX. All these changes of EANA treatments in oral cancer cells were reverted by the ROS scavenger N-acetylcysteine pretreatment. Therefore, EANA induces preferential killing, apoptosis, and DNA damage against oral cancer cells through oxidative stress.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Neoplasias Bucais/tratamento farmacológico , Estresse Oxidativo , Traqueófitas , Acetatos , Antineoplásicos Fitogênicos/uso terapêutico , Apoptose , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dano ao DNA , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/metabolismo , Neoplasias Bucais/metabolismo , Fitoterapia , Extratos Vegetais/farmacologia , Poli(ADP-Ribose) Polimerases/metabolismo , Espécies Reativas de Oxigênio/metabolismo
10.
Int J Mol Sci ; 20(12)2019 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-31208018

RESUMO

Sesquiterpene lactones constitute a major class of bioactive natural products. One of the naturally occurring sesquiterpene lactones is costunolide, which has been extensively investigated for a wide range of biological activities. Multiple lines of preclinical studies have reported that the compound possesses antioxidative, anti-inflammatory, antiallergic, bone remodeling, neuroprotective, hair growth promoting, anticancer, and antidiabetic properties. Many of these bioactivities are supported by mechanistic details, such as the modulation of various intracellular signaling pathways involved in precipitating tissue inflammation, tumor growth and progression, bone loss, and neurodegeneration. The key molecular targets of costunolide include, but are not limited to, intracellular kinases, such as mitogen-activated protein kinases, Akt kinase, telomerase, cyclins and cyclin-dependent kinases, and redox-regulated transcription factors, such as nuclear factor-kappaB, signal transducer and activator of transcription, activator protein-1. The compound also diminished the production and/expression of proinflammatory mediators, such as cyclooxygenase-2, inducible nitric oxide synthase, nitric oxide, prostaglandins, and cytokines. This review provides an overview of the therapeutic potential of costunolide in the management of various diseases and their underlying mechanisms.


Assuntos
Compostos Fitoquímicos/farmacologia , Sesquiterpenos/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico , Antioxidantes/química , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Humanos , Compostos Fitoquímicos/química , Compostos Fitoquímicos/uso terapêutico , Sesquiterpenos/química , Sesquiterpenos/uso terapêutico
11.
Food Chem Toxicol ; 132: 110644, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31252023

RESUMO

Supercritical fluid technologies offer an innovative method for food industry and drug discovery from natural sources. The aim of the study is to investigate the anti-tumor activity of piperine rich extract by supercritical fluid (SFE) from black pepper (Piper nigrum). In silico docking simulations predicted anti-tumor molecular mechanism and protein-piperine hydrophobic interactions, showing hydrogen bonds between piperine and residue Ser5 inside the ATP binding site in CDK2. Moreover, piperine interacts with peptide substrate residue Lys8 inside its binding site in Cyclin A molecule. Other predicted interaction showed piperine inside the hydrophobic groove of Bcl-xL. Confirming the docking simulation, in vitro assays with SFE (40 °C/30 MPa) showed cytotoxicity to MCF-7 cells (IC50 = 27.8 ±â€¯6.8 µg/ml) correlated to increased apoptosis. Balb/c mice-bearing Ehrlich Ascites Carcinoma (EAC) group that received the SFE (100 mg/kg/day) showed tumor growth inhibition (60%) and increased mice survival (50%), probably related to cell cycle arrest (G2/M) and increased apoptosis. In vivo treatments with SFE increased the expression of pro-apoptotic proteins (p53 and Bax), inhibited cell cycle proteins (CDK2, Cyclin A) and anti-apoptotic protein (Bcl-xL). Thus, confirming in silico predicted inhibitory interactions. These results clearly showed promising performance of the piperine-rich fraction recovered from black pepper, drawing attention to its use as complementary therapy for cancer.


Assuntos
Alcaloides/uso terapêutico , Antineoplásicos Fitogênicos/uso terapêutico , Benzodioxóis/uso terapêutico , Piperidinas/uso terapêutico , Alcamidas Poli-Insaturadas/uso terapêutico , Alcaloides/química , Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Benzodioxóis/química , Benzodioxóis/isolamento & purificação , Benzodioxóis/farmacologia , Dióxido de Carbono/química , Quinase 2 Dependente de Ciclina/química , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Humanos , Células MCF-7 , Masculino , Camundongos Endogâmicos BALB C , Simulação de Acoplamento Molecular , Piper nigrum/química , Piperidinas/química , Piperidinas/isolamento & purificação , Piperidinas/farmacologia , Alcamidas Poli-Insaturadas/química , Alcamidas Poli-Insaturadas/isolamento & purificação , Alcamidas Poli-Insaturadas/farmacologia , Extração em Fase Sólida/métodos , Proteína bcl-X/química
12.
Phytother Res ; 33(8): 2075-2082, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31157484

RESUMO

Three biflavonoids [cupressuflavone (1), amentoflavone (2), and sumaflavone (3)], four diterpenoids [13-epi-cupressic acid (4), imbricatholic acid (5), 3-hydroxy-sandaracopimaric acid (6), and dehydroabietic acid (7)], and one lignan [ß-peltatin methyl ether (8)] were isolated from the cytotoxic fractions of the extracts of the leaves of the Libyan Juniperus phoenicea L. The structures of these compounds were elucidated by spectroscopic means. Cytotoxicity of compounds 1-6 were assessed against the human lung cancer cell line A549 using the MTT assay. Compounds 1 and 3 showed cytotoxicity against the A549 cells (IC50  = 65 and 77 µM, respectively), whereas compound 2 did not show any activity. Diterpenes 4-6 exhibited weak cytotoxicity against the A549 cells with the IC50 values of 159, 263, and 223 µM, respectively. The cytotoxicity of each compound was compared with the anticancer drug, etoposide (IC50  = 61 µM). Cupressuflavone (1) was evaluated also for cytotoxicity against both the human PC3 cancer cell line and the normal prostate cell line (PNT2), and this compound revealed a high degree of cytotoxic selectivity towards the prostate cancer cells (PC3), with IC50 value of 19.9 µM, without any evidence of cytotoxicity towards the normal prostate cell line (PNT2).


Assuntos
Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/uso terapêutico , Biflavonoides/química , Diterpenos/química , Juniperus/química , Neoplasias/tratamento farmacológico , Folhas de Planta/química , Humanos
13.
J Craniofac Surg ; 30(4): 1191-1193, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31166264

RESUMO

Langerhans cell histiocytosis (LCH) commonly affects the craniofacial skeleton and prognosis depends on location, extension, and recurrence of the disease. The aim of our study is to better define the treatment of single craniofacial lesions, as to date different treatment modalities have been suggested and recurrence rates for both unifocal and multifocal bony lesion range between 10% and 70%. Between 2000 and 2014, we retrospectively reviewed clinical findings, anatomic location, extent of the disease, therapy, and outcomes in 24 pediatric patients with histologically confirmed LCH. Seventeen patients (67%) had craniofacial involvement, of which 13 had single system involvement and 4 had multisystem involvement. Eight patients (33%) had no craniofacial involvement. Eleven patients affected by unifocal cranial lesions were treated with resection and reconstruction. One patient with a unifocal mastoid lesion was treated with chemotherapy alone (vinblastine and prednisone). Four patients with mandible lesions were treated with curettage alone.There were no recurrences in patients treated with excision alone. One patient (25%) treated with curettage recurred. Two patients with diffuse disease manifested organ dysfunction and diabetes insipidus. Chemotherapy was tolerated in 12 patients treated.Our findings suggest that resection of isolated LCH lesions of the cranium is safe and chemotherapy is effective and well tolerated for nonsurgical cases.


Assuntos
Curetagem , Histiocitose de Células de Langerhans/terapia , Prednisona/uso terapêutico , Crânio/cirurgia , Vimblastina/uso terapêutico , Adolescente , Antineoplásicos Fitogênicos/uso terapêutico , Criança , Pré-Escolar , Feminino , Glucocorticoides/uso terapêutico , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos , Crânio/transplante
14.
Int J Mol Sci ; 20(11)2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31159437

RESUMO

Cancer diseases have the leading position in human mortality nowadays. The age of oncologic patients is still decreasing, and the entire scientific society is eager for new ways to fight against cancer. One of the most discussed issues is prevention by means of natural substances. Resveratrol is a naturally occurring plant polyphenol with proven antioxidant, anti-inflammatory, and anticancer effects. Tumor cells display specific changes in the metabolism of various lipids. Resveratrol alters lipid metabolism in cancer, thereby affecting storage of energy, cell signaling, proliferation, progression, and invasiveness of cancer cells. At the whole organism level, it contributes to the optimal metabolism extent with respect to the demands of the organism. Thus, resveratrol could be used as a preventive and anticancer agent. In this review, we focus on some of the plethora of lipid pathways and signal molecules which are affected by resveratrol during carcinogenesis.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Neoplasias/metabolismo , Resveratrol/farmacologia , Animais , Antineoplásicos Fitogênicos/uso terapêutico , Colesterol/metabolismo , Ensaios Clínicos como Assunto , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Redes e Vias Metabólicas/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Neoplasias/etiologia , Espécies Reativas de Oxigênio/metabolismo , Resveratrol/uso terapêutico , Resultado do Tratamento
15.
Phytomedicine ; 59: 152771, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31055230

RESUMO

BACKGROUND: The multidrug resistance (MDR) phenotype encounters a major challenge to the success of established chemotherapy in cancer patients. We hypothesized that cytotoxic medicinal plants with novel phytochemicals can overcome MDR and kill MDR-cells with similar efficacy as drug sensitive cells. PURPOSE: We evaluated plant extracts from an unexplored ecosystem in Egypt with unusual climate and nutrient conditions for their activity against sensitive and multidrug-resistant cancer cell lines. MATERIAL AND METHODS/STUDY DESIGN: Methylene chloride: methanol (1:1) and methanol: H2O (7:3) extracts of 40 plants were prepared resulting in a sum of 76 fraction containing compounds with varying polarity. The resazurin reduction assay was employed to evaluate the cytotoxicity of these extracts on five matched pairs of drug-sensitive and their drug-resistant cell lines. Flow cytometry and Western blotting was used to determine cell cycle analyses, apoptosis, and autophagy. Reactive oxygen species (ROS) were measured spectrophotometrically. RESULTS: Extracts derived from Withania obtusifolia (WO), Jasonia candicans (JC), Centaurea lippii (CL), and Pulicaria undulata (PU) were the most active ones among 76 extracts from 40 Egyptian medicinal plants. They showed a significant reduction of cell viability on drug-sensitive CCRF-CEM leukemia cell line with IC50 values less than 7 µg/ml. Low cross-resistance degrees were observed in multidrug-resistant CEM/ADR5000 cells towards CL (1.82-fold) and JC (6.09-fold). All other drug-resistant cell lines did not reveal cross-resistance to the four extracts. Further mechanistic assessment have been studied for these four extracts. CONCLUSION: The methylene chloride: methanol (1:1) fractions of WO, JC, CL, and PU are promising cytotoxic extracts that could be used to combat MDR cancer cells through different cell death pathways.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Magnoliopsida/química , Neoplasias/tratamento farmacológico , Compostos Fitoquímicos/farmacologia , Fitoterapia , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Antineoplásicos Fitogênicos/uso terapêutico , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Centaurea/química , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Egito , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Compostos Fitoquímicos/uso terapêutico , Extratos Vegetais/uso terapêutico , Pulicaria/química , Espécies Reativas de Oxigênio/metabolismo , Withania/química
16.
Am J Vet Res ; 80(6): 601-606, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31140850

RESUMO

OBJECTIVE: To evaluate the efficacy of maropitant and loperamide for the prevention and reduction of adverse gastrointestinal effects associated with administration of paclitaxel to dogs with cancer. ANIMALS: 168 dogs with cancer. PROCEDURES: The study comprised 2 phases. For phase 1, dogs in the intervention group were administered maropitant and loperamide followed by paclitaxel. Outcomes were compared with those for a control group that received only maropitant and paclitaxel. For phase 2, all dogs of phase 1 that did not receive maropitant and loperamide and that had adverse gastrointestinal effects were enrolled; they received maropitant and loperamide and another dose of paclitaxel. RESULTS: In phase 1, significantly fewer dogs in the intervention group had adverse effects. For dogs that had adverse effects, the intervention group had a lower severity of lack of appetite and lethargy. Also, adverse effects for dogs in the intervention group were of significantly shorter duration than for the control group. In phase 2, significant reductions in adverse effects were observed after administration of maropitant and loperamide. In those dogs that still had adverse effects after administration of maropitant and loperamide, there was a significant reduction in severity of signs of nausea and lethargy. CONCLUSIONS AND CLINICAL RELEVANCE: A combination of maropitant and loperamide was found to be safe for use and effective for reducing or preventing signs of paclitaxel-induced gastrointestinal effects in dogs.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Doenças do Cão/tratamento farmacológico , Loperamida/uso terapêutico , Neoplasias/veterinária , Paclitaxel/efeitos adversos , Quinuclidinas/uso terapêutico , Animais , Antidiarreicos/uso terapêutico , Antieméticos/uso terapêutico , Antineoplásicos Fitogênicos/efeitos adversos , Diarreia/induzido quimicamente , Diarreia/prevenção & controle , Diarreia/veterinária , Cães , Quimioterapia Combinada , Feminino , Masculino , Neoplasias/tratamento farmacológico , Paclitaxel/uso terapêutico , Distribuição Aleatória , Vômito/induzido quimicamente , Vômito/prevenção & controle , Vômito/veterinária
17.
Int J Mol Sci ; 20(9)2019 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-31075954

RESUMO

Multiple myeloma (MM)-a common hematologic malignancy of plasma cells-accounts for substantial mortality and morbidity rates. Due to the advent of novel therapies such as immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs), and monoclonal antibodies (mAbs), response rates were increased and free survival and overall survival have been elevated. However, adverse events including toxicity, neuropathy or continuous relapse are still problems. Thus, development of novel drugs which have less side effects and more effective is needed. This review aims to recapitulate the pharmacologic anti-MM mechanisms of various phytochemicals, elucidating their molecular targets. Keywords related to MM and natural products were searched in PUBMED/MEDLINE. Phytochemicals have been reported to display a variety of anti-MM activities, including apoptosis, cell cycle arrest, antiangiogenesis, and miRNA modulation. Some phytochemicals sensitize the conventional therapies such as dexamethasone. Also, there are clinical trials with phytochemicals such as agaricus, curcumin, and Neovastat regarding MM treatment. Taken together, this review elucidated and categorized the evidences that natural products and their bioactive compounds could be potent drugs in treating MM.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Compostos Fitoquímicos/uso terapêutico , Animais , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Humanos , Mieloma Múltiplo/patologia , Neovascularização Patológica/tratamento farmacológico , Compostos Fitoquímicos/farmacologia
18.
Int J Mol Sci ; 20(10)2019 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-31126043

RESUMO

Phytochemicals are known to benefit human health by modulating various cellular processes, including cell proliferation, apoptosis, and inflammation. Due to the potential use of phytochemicals as therapeutic agents against human diseases such as cancer, studies are ongoing to elucidate the molecular mechanisms by which phytochemicals affect cellular functions. It has recently been shown that phytochemicals may regulate the expression of microRNAs (miRNAs). MiRNAs are responsible for the fine-tuning of gene expression by controlling the expression of their target mRNAs in both normal and pathological cells. This review summarizes the recent findings regarding phytochemicals that modulate miRNA expression and promote human health by exerting anticancer, photoprotective, and anti-hepatosteatosis effects. Identifying miRNAs modulated by phytochemicals and understanding the regulatory mechanisms mediated by their target mRNAs will facilitate the efforts to maximize the therapeutic benefits of phytochemicals.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Fígado Gorduroso/tratamento farmacológico , MicroRNAs/genética , Neoplasias/tratamento farmacológico , Compostos Fitoquímicos/uso terapêutico , Substâncias Protetoras/uso terapêutico , Animais , Antineoplásicos Fitogênicos/farmacologia , Fígado Gorduroso/genética , Fígado Gorduroso/prevenção & controle , Regulação da Expressão Gênica/efeitos dos fármacos , Promoção da Saúde , Humanos , Neoplasias/genética , Neoplasias/prevenção & controle , Compostos Fitoquímicos/farmacologia , Substâncias Protetoras/farmacologia
19.
Food Chem Toxicol ; 130: 1-11, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31054290

RESUMO

Natural products derived from fruits have multiple antitumor potential. However, very few have been developed for clinical therapy, due to the limited efficiency or insufficient study of their mechanism. Since lung cancer is the most common cancer in the world, there is still need to explore novel compounds but their molecular mechanisms remain elusive. In this study, a new compound Final-2 was synthesized. Final-2 exhibited antitumor activity in A549 cells by promoting apoptosis and blocking autophagy. Moreover, Final-2 significantly induced G0/G1 cycle arrest and inhibited cell malignancy. Intracellular molecular targets investigation showed that Final-2 inhibited the Gluts, which resulted in downregulation of glucose metabolism and the oncogene c-Myc and Kras expression in vitro. However, according the autophagy inhibitor CQ and Kras inhibitors test, low concentration of Final-2 showed some controversial effects. In A549 xenograft mice model, 10 mg/kg and 20 mg/kg of Final-2 showed no and partial tumor inhibition, respectively. Moreover, a high dose of Final-2 induced serious liver necrosis. Therefore, the results indicated that even though Final-2 was efficient in suppressing the cancer cell growth in vitro, it failed to inhibit tumors in vivo and showed significant liver toxicity, which was its limitation as a potential antitumor drug.


Assuntos
Adenocarcinoma de Pulmão/tratamento farmacológico , Antineoplásicos Fitogênicos/uso terapêutico , Apoptose/efeitos dos fármacos , Glicólise/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Experimentais/tratamento farmacológico , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular , Descoberta de Drogas , Frutas/química , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , Camundongos Nus , Moraceae/química , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Phytother Res ; 33(7): 1794-1804, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30993793

RESUMO

Cloves (Syzygium aromaticum), a traditional Chinese medicinal herb, displays broad biological activity. In the present study, the aqueous extract of clove (AEC) was prepared, and its anticancer affects were studied. 3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetra-zolium (MTS) analysis revealed that AEC was able to inhibit cancer cell growth in vitro on several cancer cell lines; the IC50 is around 150 µg/ml for human pancreatic ASPC-1 and human colon HT-29 cancer cells. Treatment of the cancer cells with AEC also diminished the colony formation significantly in both human pancreatic ASPC-1 cancer cells and human colon HT-29 cancer cells. In vivo study revealed that AEC inhibited the tumor growth significantly in HT-29 xenograft mice model. Transmission electron microscope, flow cytometry assay, and fluorescence microscope analysis confirmed that AEC is capable of inducing cell autophagy. Further study showed that AMPK/ULK pathway plays an important role in AEC-induced autophagy in cancer cells. Analysis of AEC components was performed by liquid chromatograph mass spectrometer approach, and more than nine constitutes were identified in AEC fraction. The study provides evidence that AEC has potential to be developed as a novel anticancer agent or as an adjuvant in cancer chemotherapy.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Syzygium , Animais , Autofagia/efeitos dos fármacos , Linhagem Celular Tumoral , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Proteínas Serina-Treonina Quinases/metabolismo
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