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1.
Mol Biol Rep ; 51(1): 592, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38683376

RESUMO

PURPOSE: Ferula gummosa Boiss. is a well-known and valuable medicinal plant in Iran. Research has shown that this plant has several pharmacological properties, including anti-bacterial, anti-cancer and etc. In the present study, we investigated the cytotoxic properties of F. gummosa Boiss. extract in MCF-7 breast adenocarcinoma cells. METHODS: The cytotoxicity and pro-apoptotic properties of the extract were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) test and propidium iodide (PI) stained cells, respectively. Apoptosis and necrosis were evaluated by annexin V-PI staining. The levels of reactive oxygen species (ROS),malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) was determined to evaluate oxidative stress. The cell migration and the gene expression were assessed by scratch assay and quantitative real-time polymerase chain reaction (q-RT-PCR), respectively. RESULTS: The extract of F. gummosa decreased the viability and cell cycle progression of MCF-7 cells by inducing apoptosis and necrosis, increasing ROS and MDA levels, and decreasing GSH levels and SOD activity. It also lowered the cells' migration capability by enhancing p53 mRNA levels and reducing MMP-9 mRNA expression. CONCLUSION: F. gummosa exhibited pro-apoptotic, anti-proliferative, and anti-metastatic effects on MCF-7 cells. It is therefore recommended that detailed future research be done on different parts of the plant or its secondary metabolites to find anti-cancer lead compounds.


Assuntos
Adenocarcinoma , Apoptose , Neoplasias da Mama , Ferula , Extratos Vegetais , Espécies Reativas de Oxigênio , Humanos , Ferula/química , Apoptose/efeitos dos fármacos , Células MCF-7 , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Extratos Vegetais/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Feminino , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Adenocarcinoma/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Glutationa/metabolismo , Superóxido Dismutase/metabolismo , Proliferação de Células/efeitos dos fármacos , Linhagem Celular Tumoral , Malondialdeído/metabolismo , Ciclo Celular/efeitos dos fármacos
2.
Biogerontology ; 24(5): 801-812, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37606875

RESUMO

Bone marrow mesenchymal stem cells (BM-MSCs) have a momentous function in the composition of the bone marrow microenvironment because of their many valuable properties and abilities, such as immunomodulation and hematopoiesis. The features and actions of MSCs are influenced by senescence, which may be affected by various factors such as nutritional/micronutrients status, e.g., vitamin D. This study aimed to examine the effects of a high-calorie diet (HCD) with/without vitamin D on BM-MSCs senescence. In the first phase, 48 middle-aged rats were fed a normal chow diet (NCD, n = 24) and an HCD (n = 24) for 26 weeks. Afterward, the rats in each group were randomly divided into three equal subgroups. Immediately, eight-rat from each diet group were sacrificed to assess the HCD effects on the first phase measurements. In the second phase, the remaining 4 groups of rats were fed either NCD or HCD with (6 IU/g) or without vitamin D (standard intake: 1 IU/g); in other words, in this phase, the animals were fed (a) NCD, (b) NCD plus vitamin D, (c) HCD, and (d) HCD plus vitamin D for 4 months. BM-MSCs were isolated and evaluated for P16INK4a, P38 MAPK, and Bmi-1 gene expression, reactive oxygen species (ROS) levels, SA-ß-gal activity, and cell cycle profile at the end of both phases. After 26 weeks (first phase), the ROS level, SA-ß-gal-positive cells, and cells in the G1 phase were significantly higher in HCD-fed rats than in NCD-fed ones (P < 0.05). HCD prescription did not significantly affect cells in the S and G2 phases (p > 0.05). Compared with the NCD-fed animals, P16INK4a and P38 MAPK gene expression were up-regulated in the HCD-fed animals; also, Bmi-1 gene expression was down-regulated (P < 0.05). BM-MSCs from vitamin D-treated rats (second phase) exhibited reduced mRNA levels of P16INK4a and P38 MAPK genes and increased Bmi-1 mRNA levels (all P < 0.05). Vitamin D prescription also declined the percentage of SA-ß-gal-positive cells, ROS levels, and the cells in the G1 phase and increased the cells in the S phase in both NCD and HCD-fed animals (P < 0.05). The reduction of the cells in the G2 phase in rats fed with an NCD plus vitamin D was statistically non-significant (P = 0.128) and significant in HCD plus vitamin D rats (P = 0.002). HCD accelerates BM-MSCs senescence, and vitamin D reduces BM-MSCs senescence biomarkers.


Assuntos
Células-Tronco Mesenquimais , Doenças não Transmissíveis , Masculino , Ratos , Animais , Vitamina D , Ratos Wistar , Inibidor p16 de Quinase Dependente de Ciclina , Espécies Reativas de Oxigênio
3.
Cell Biol Int ; 45(10): 2031-2044, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34293823

RESUMO

Extracellular vesicles (EVs) either as endocytic or plasma membrane-emerged vesicles play pivotal role in cell-to-cell communication. Due to the bioactive molecules transformation, lymphoma cell-derived vesicles can alter a recipient cell's function and contribute to signal transduction and drug resistance. These vesicles by acting not only in tumor cells but also in tumor-associated cells have important roles in tumor growth and invasion. On the other hand, the total protein level of circulating exosomes reveals the disease stage, tumor burden, response to therapy, and survival. In residual disease, leukemic blasts are undetectable in the bone marrow by conventional methods but exosomal proteins are elevated significantly. In this manner, new methods for measuring exosomes and exosomal components are required. In this review, we try to reveal the concealed role of EVs in hematological malignancies besides therapeutic potentials.


Assuntos
Comunicação Celular , Vesículas Extracelulares/transplante , Neoplasias Hematológicas/terapia , Medicina Regenerativa , Animais , Humanos
4.
Molecules ; 26(6)2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33802011

RESUMO

The use of naturally occurring materials in biomedicine has been increasingly attracting the researchers' interest and, in this regard, gum tragacanth (GT) is recently showing great promise as a therapeutic substance in tissue engineering and regenerative medicine. As a polysaccharide, GT can be easily extracted from the stems and branches of various species of Astragalus. This anionic polymer is known to be a biodegradable, non-allergenic, non-toxic, and non-carcinogenic material. The stability against microbial, heat and acid degradation has made GT an attractive material not only in industrial settings (e.g., food packaging) but also in biomedical approaches (e.g., drug delivery). Over time, GT has been shown to be a useful reagent in the formation and stabilization of metal nanoparticles in the context of green chemistry. With the advent of tissue engineering, GT has also been utilized for the fabrication of three-dimensional (3D) scaffolds applied for both hard and soft tissue healing strategies. However, more research is needed for defining GT applicability in the future of biomedical engineering. On this object, the present review aims to provide a state-of-the-art overview of GT in biomedicine and tries to open new horizons in the field based on its inherent characteristics.


Assuntos
Tragacanto/química , Tragacanto/metabolismo , Tragacanto/farmacologia , Antibacterianos/química , Astragalus gummifer/metabolismo , Materiais Biocompatíveis/química , Sistemas de Liberação de Medicamentos/métodos , Embalagem de Alimentos/métodos , Nanofibras/química , Poliésteres/química , Medicina Regenerativa/métodos , Engenharia Tecidual/métodos , Alicerces Teciduais/química , Cicatrização/efeitos dos fármacos
5.
J Cell Biochem ; 121(2): 1778-1789, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31642100

RESUMO

3-Acetyl-11-keto-ß-boswellic acid (AKBA), a pentacyclic triterpenic acid present in gum resin of Boswellia serrata, has been found to possess antioxidant and neuroprotective properties. In this study, we aimed to examine protective properties of AKBA against glutamate-induced neuronal injury. To investigate the effects of AKBA (2.5-10 µM) on glutamate injury in neuron-like cells PC12 and N2a, two treatment regimens (incubation for 2 or 0 hours before glutamate exposure) were used. Then, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method was used to determine viability of the cells. Cellular redox status was evaluated using fluorimetry and comet assays. Annexin V/propidium iodide double staining and Western blot analysis of relative apoptotic proteins were conducted. Based on the results, 24 hours incubation with glutamate (8 mM) increased the cell mortality of PC12 and N2a (P < .001). However, AKBA (2.5-10 µM) enhanced the cell viability in both treatment regimens (P < .001). Also co- and pretreatment with AKBA significantly attenuated lipid peroxidation, reactive oxygen species production, and DNA injury (P < .05 and P < .001). AKBA also restored the activity of cellular superoxide dismutase under glutamate toxicity; this effect was seen to be more significant during the pretreatment regimen (P < .001). Moreover, Western blot analysis indicated that AKBA inhibited glutamate-induced programmed cell death through depressing the elevation of the expression ratio of Bax/Bcl-2 and cleaved-caspase-3 proteins, concentration-dependently. Overall, the present findings suggest the neuroprotective activities of AKBA against glutamate-induced cell injury probably by inhibiting oxidative damage and reducing apoptotic cell death.


Assuntos
Neoplasias das Glândulas Suprarrenais/tratamento farmacológico , Apoptose/efeitos dos fármacos , Ácido Glutâmico/toxicidade , Neuroblastoma/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Feocromocitoma/tratamento farmacológico , Triterpenos/farmacologia , Neoplasias das Glândulas Suprarrenais/induzido quimicamente , Neoplasias das Glândulas Suprarrenais/patologia , Animais , Peroxidação de Lipídeos/efeitos dos fármacos , Camundongos , Neuroblastoma/induzido quimicamente , Neuroblastoma/patologia , Células PC12 , Feocromocitoma/induzido quimicamente , Feocromocitoma/patologia , Ratos
6.
J Surg Res ; 248: 171-181, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31923833

RESUMO

BACKGROUND: Angiotensin II receptor blockers (ARBs) have a potential role in reducing inflammation and fibrosis. We have integrated systems and molecular biology approaches to investigate the therapeutic potential of ARBs in preventing postsurgical adhesion band formation. MATERIAL AND METHODS: we have followed the ARRIVE guidelines point by point during experimental studies. Telmisartan (1 and 9 mg/kg), valsartan (1 and 9 mg/kg), and losartan (1 and 10 mg/kg) were administered intraperitoneally in different groups of male albino Wistar rat. After 7 d of treatment, macroscopic evidence and score of fibrotic bands based on scaling methods was performed. Moreover, the anti-inflammatory and antifibrosis effects of telmisartan on reduction of fibrotic bands were investigated by using histopathology, ELISA, and real-time polymerase chain reaction methods. RESULTS: Telmisartan, but not losartan or valsartan, prevented the frequency as well as the stability of adhesion bands. Telmisartan appears to elicit anti-inflammatory responses by attenuating submucosal edema, suppressing proinflammatory cytokines, decreasing proinflammatory cell infiltration, and inhibiting oxidative stress at the site of peritoneal surgery. We also showed that telmisartan prevents fibrotic adhesion band formation by reducing excessive collagen deposition and suppression of profibrotic genes expression at the peritoneum adhesion tissues. CONCLUSIONS: These results support the potential application of telmisartan in preventing postsurgical adhesion band formation by inhibiting key pathologic responses of inflammation and fibrosis in postsurgery patients.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/administração & dosagem , Telmisartan/administração & dosagem , Aderências Teciduais/prevenção & controle , Animais , Avaliação Pré-Clínica de Medicamentos , Injeções Intraperitoneais , Masculino , Distribuição Aleatória , Ratos Wistar
7.
Planta Med ; 86(6): 405-414, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32097974

RESUMO

Postoperative adhesions are regarded as the major complication following abdominal surgery. Rosmarinus officinalis has shown antioxidative and anti-inflammatory effects. Therefore, we aimed to assess the influence of 70% v/v hydro-ethanolic extract of the aerial parts of R. officinalis against postoperative abdominal adhesions in a rat model. Forty-eight male Wistar rats (190 ± 20 g) were divided into six groups of eight: group 1 = normal group, without any surgical procedures, group 2 = control group, group 3 = vehicle group, and groups 3, 4, and 5 = experimental groups receiving 2 mL of 4, 2, or 1% w/v R. officinalis treatment. Adhesion levels were macroscopically examined. Additionally, the levels of inflammatory cytokines (interleukin-6, interleukin-1ß, and TNF-α), growth factors (transforming growth factor-ß1, and vascular endothelial growth factor), oxidative (NO, nitric oxide and MDA, malondialdehyde), and antioxidative (GSH, glutathione) factors were evaluated. Our results revealed that the adhesion score, interleukin-6, interleukin-1ß, TNF-α, transforming growth factor-ß1, vascular endothelial growth factor, NO, and MDA levels were significantly increased in the vehicle group, while the GSH level was diminished. R. officinalis treatment notably ameliorated the adhesion score following postoperative abdominal adhesions compared with the vehicle group. Our results also revealed that R. officinalis markedly reduced inflammatory cytokines, oxidative factors, fibrosis, and angiogenesis biomarkers, whereas it increased the antioxidative factor. Therefore, R. officinalis may be a potential candidate for the management of postoperative peritoneal adhesion.


Assuntos
Rosmarinus , Animais , Masculino , Lavagem Peritoneal , Extratos Vegetais , Ratos , Ratos Wistar , Aderências Teciduais , Fator A de Crescimento do Endotélio Vascular
8.
Immunopharmacol Immunotoxicol ; 42(3): 246-254, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32248717

RESUMO

Background and purpose: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation and joint destruction. Excessive proliferation of fibroblast-like synoviocytes (FLS) and over-expression of angiogenic factors play a crucial role in pannus formation and joint destruction in RA. Clarification of the role of cholinergic agonists in modulation of inflammation and immune system reactions is progressively ongoing. In this study, the anti-angiogenic effect of two cholinergic agonists, nicotine and ARR17779, on human FLS, and monocytic cell lines (U937) was evaluated.Experimental approach: The cells were cultured in DMEM supplemented with 10% FBS and treated with different doses of nicotine and ARR17779 in the presence of TNF-α, LPS, and IFN-γ. After 48 h, cell number was counted in different groups. After RNA extraction, cDNA was synthesized and the expression of VEGF and MMPs has been evaluated by real-time PCR using specific primers and probes. VEGF was assayed in U937 cell line supernatant using ELISA method.Key results: Both nicotine and ARR17779 inhibited FLS and U937 cell proliferation. Cholinergic agonists reduced the expression of MMPs and VEGF. VEGF level in supernatant of U937 cells treated with cholinergic agonists was also reduced.Conclusion and implications: Our results suggest that cholinergic agonists can modulate pathological conditions related to pannus formation in in-vitro conditions. Based on these results, cholinergic agonists can be considered as novel therapeutic options in RA. Further animal studies are needed before introducing these agents into clinical uses.


Assuntos
Proliferação de Células/efeitos dos fármacos , Agonistas Colinérgicos/farmacologia , Fibroblastos/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Metaloproteinases da Matriz/genética , Monócitos/efeitos dos fármacos , Sinoviócitos/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/genética , Técnicas de Cultura de Células , Citocinas/metabolismo , Relação Dose-Resposta a Droga , Fibroblastos/imunologia , Humanos , Monócitos/imunologia , Sinoviócitos/imunologia , Células U937 , Receptor Nicotínico de Acetilcolina alfa7/agonistas
9.
Can J Physiol Pharmacol ; 96(2): 137-144, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28772088

RESUMO

Clinical use of zoledronate is accompanied by osteonecrosis of the jaw but the pathogenesis is not well understood. We assumed that zoledronate may have cytotoxicity against stem cells of the oral cavity and in this way helps to initiate or promote osteonecrosis. Dental pulp stem cells (DPSCs) and gingival fibroblasts (GFs) were isolated from volunteers who were undergoing a third molar extraction. The proliferation of DPSCs and GFs was evaluated using the thiazolyl blue tetrazolium bromide assay. The effect of zoledronate on apoptosis was determined by propidium iodide staining and Western blotting analysis. Incubation with zoledronate for 72 h and 7 days significantly decreased proliferation of DPSCs and GFs at concentrations of more than 0.4 µmol/L (p < 0.001). The IC50 of zoledronate was lower for DPSCs than for GFs (0.92 versus 3.5 µmol/L for 7 days of treatment). After 72 h of treatment with zoledronate, the percentage of apoptotic DPSCs significantly increased, which was accompanied by an increased level of pro-apoptotic proteins caspase-3 and Bax and decreased the level of the anti-apoptotic protein Bcl-2. In conclusion, zoledronate has anti-proliferative and pro-apoptotic effects in DPSCs. These effects may be involved in promoting zoledronate-induced osteonecrosis and suggest an unfavorable impact of this drug on regenerative potentials of the body stem cells.


Assuntos
Apoptose/efeitos dos fármacos , Polpa Dentária/citologia , Difosfonatos/farmacologia , Imidazóis/farmacologia , Células-Tronco/citologia , Biomarcadores/metabolismo , Caspase 3/metabolismo , Proliferação de Células/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Citometria de Fluxo , Gengiva/citologia , Humanos , Células-Tronco/efeitos dos fármacos , Células-Tronco/metabolismo , Ácido Zoledrônico , Proteína X Associada a bcl-2/metabolismo
10.
Nanomedicine ; 14(5): 1707-1718, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29753127

RESUMO

Umbilical cord blood (CB) can be used as an alternative source of hematopoietic stem cells (HSCs) for transplantation in hematological and non-hematological disorders. Despite several recognized advantages the limited cell number in CB one unit still restricts its clinical use. The success of transplantation greatly depends on the levels of total nucleated cell and CD34+ cell counts. Thus, many ex vivo strategies have been developed within the last decade in order to solve this obstacle, with more or less success, mainly determined by the degree of difficulty related with maintaining HSCs self-renewal and stemness properties after long-term expansion. Different research groups have developed very promising and diverse CB-derived HSC expansion strategies using nanofiber scaffolds. Here we review the state-of-the-art of nanofiber technology-based CB-derived HSC expansion.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Sangue Fetal/citologia , Nanofibras/administração & dosagem , Nanofibras/química , Proliferação de Células , Humanos
11.
Pediatr Blood Cancer ; 64(7)2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27905684

RESUMO

Umbilical cord blood (CB) can be used as an alternative hematopoietic stem cell source for transplantation in hematological malignancy and blood disorders. The success of transplantation is highly related to the levels of total nucleated cell and CD34+ cell counts. The evaluation of optimal conditions can decrease the rate of graft rejection due to low cell count and increases the quality of CB units (CBUs) in the blood bank and the success rate of engraftment. To this end, we review the maternal and infant parameters affecting the quality and quantity of CBUs.


Assuntos
Sangue Fetal/citologia , Fenômenos Reprodutivos Fisiológicos , Feminino , Humanos , Recém-Nascido , Mães
12.
Cell Mol Biol (Noisy-le-grand) ; 63(11): 17-22, 2017 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-29208170

RESUMO

Ferula species known for its oleo-resins that are recognized valuable industrial crops and food products. In this study, we examined the level of cellular oxidants, cytotoxicity, apoptosis and differentiation induced by oleo resin gum from Ferula gummosa (30-250 µg/mL), as well as Arsenic trioxide (50 µM, as positive control), in leukemic (NB4 and HL-60 cells) and normal polymorph nuclear cells during 72 h. Resazurin assay was used to determine cell viability following treatment with F. gummosa (30-250 µg/mL). Intracellular reactive oxygen species was measured by fluorimetry using carboxy 2', 7'-dichlorofluorescein diacetate. Apoptotic cells were evaluated using PI staining of DNA fragmentation by flow cytometry (sub-G1 peak). Differentiation of cells evaluated by Giemsa staining and Nitro Blue Tetrazolium reduction. F. gummosa showed a concentration-dependent suppression in cell survival with IC50 values of 41.8 µg/mL for HL60 and 59.2 µg/mL for NB4 cells after 72 h treatment. ROS formation and apoptotic cells were concentration-dependently increased following treatment with F. gummosa, similar to As2O3. F. gummosa did not induce differentiation of leukemic cells towards granulocytic pattern. The resin did not have toxic effect on PMN cells (<800 µg/mL). In conclusion, the present study demonstrated that F. gummosa induced apoptosis through ROS mechanism on leukemic cells as a concentration and time dependent manner. The precise signaling pathway by which F. gummosa induce apoptosis needs further research.


Assuntos
Apoptose/fisiologia , Ferula/química , Leucemia/metabolismo , Extratos Vegetais/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Apoptose/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Células Cultivadas , Células HL-60 , Humanos , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia
13.
Toxicol Mech Methods ; 25(8): 614-21, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26330000

RESUMO

CONTEXT: Over expression of renin-angiotensin system (RAS) and nuclear factor-kappaB (NF-κB) has a major role in many cancers. It has been suggested that some angiotensin receptor blockers (ARBs) could reduce the proliferation of cancer cells. The role of NF-κB pathway has been documented in cell proliferation. OBJECTIVE: In this study, the role of angiotensin II and NF-κB pathway in human cervical cancer cell line (HeLa) proliferation was studied using olmesartan (as a novel Ag II antagonist) and Bay11-7082 (as NF-κB inhibitor). MATERIALS AND METHODS: HeLa cells were treated with different concentrations of olmesartan and Bay11-7082. Cell proliferation was determined after 24, 48, and 72 h by MTT assay. Synergistic activity of olmesartan with Bay11-7082 was analyzed with Compusyn software. Apoptotic cells were determined using PI staining of DNA fragmentation. RESULTS: Cell viability decreased with olmesartan and Bay11-7082 in HeLa cells by 24, 48 and 72 h. Olmesartan had synergistic activity with Bay11-7082 and combinations of olmesartan with Bay11-7082 decreased cell viability as compared with single agent treatments. Olmesartan and Bay11-7082 induced a sub-G1 peak in flow cytometry histogram of treated cells indicating that apoptotic cell death is involved in olmesartan and Bay11-7082-induced toxicity. DISCUSSION AND CONCLUSION: Results imply that olmesartan and Bay11-7082 inhibit the growth of HeLa cells as a concentration- and time-dependent mode and they have synergistic activity. Results show that RAS and NF-κB pathway blockade lead to significant cytotoxicity against tumor cell line. So, ARBs and NF-κB pathway inhibitors could be considered as good anti-cancer agents in cervix carcinoma after further studies.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Imidazóis/farmacologia , NF-kappa B/antagonistas & inibidores , Nitrilas/farmacologia , Sulfonas/farmacologia , Tetrazóis/farmacologia , Neoplasias do Colo do Útero/tratamento farmacológico , Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos , Bloqueadores do Receptor Tipo 1 de Angiotensina II/química , Antineoplásicos/efeitos adversos , Antineoplásicos/química , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sinergismo Farmacológico , Feminino , Fase G1/efeitos dos fármacos , Células HeLa , Humanos , Imidazóis/efeitos adversos , Imidazóis/agonistas , Concentração Inibidora 50 , Cinética , Masculino , NF-kappa B/metabolismo , Nitrilas/efeitos adversos , Nitrilas/agonistas , Sulfonas/efeitos adversos , Sulfonas/agonistas , Tetrazóis/efeitos adversos , Tetrazóis/agonistas , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia
14.
Bioorg Khim ; 41(2): 227-34, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26165130

RESUMO

In vitro antiproliferative activities of some pyrimido[4,5-e][1,3,4]oxadiazine and [1,2,4]triazolo[4',3':1,2]pyrimido[4,5-e][1,3,4]oxadiazine derivatives were examined in human malignant cancer cell lines. All synthesized compounds inhibited the growth of malignant cells in a dose dependent manner, but among them 1,5,7-trimethyl-3-phenyl-1H-[1,2,4]triazolo[4',3':1,2]pyrimido[4,5-e][1,3,4]oxadiazine and [(1,5-dimethyl-3-phenyl-1H-[1,2,4]triazolo[4',3':1,2]pyrimido[4,5-e][1,3,4]oxadiazin-7-yl)sulfanyl]acetonitrile, both with triazole moiety, were found to be more effective than other compounds; they also induced a sub-G1 peak in the flow cytometry histogram of treated cells compared to controls, indicating that apoptotic cell death is involved in toxicity they induce. The results showed that compounds with triazole moiety fused to pyrimido[4,5-e] [1,3,4]oxadiazine derivatives are more active than those bearing chlorine or pyrrolidine groups at C-7 position.


Assuntos
Antineoplásicos , Citotoxinas , Neoplasias/tratamento farmacológico , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Citotoxinas/síntese química , Citotoxinas/química , Citotoxinas/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Humanos
15.
Nutr Cancer ; 66(3): 424-34, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24571090

RESUMO

Lavender (Lavandula angustifolia Mill.) is a bush-like shrub from Lamiaceae. The herb has been used in alternative medicine for several centuries. In this study, the cytotoxicity and the mechanisms of cell death induced by 3 different extracts of aerial parts and the essential oil of L. angustifolia were compared in normal and cancerous human cells. Malignant (HeLa and MCF-7 cell lines) and nonmalignant (human fibroblasts) cells were incubated with different concentrations of the plant extracts. Cell viability was quantified by MTS assay. Apoptotic cells were determined using propidium iodide staining of DNA fragmentation by flow cytometry (sub-G1 peak). The molecules as apoptotic signal translation, including Bax and cleaved PARP, were identified by Western blot. Ethanol and n-hexane extracts and essential oil exhibited significant cytotoxicity to malignant cells but marginal cytotoxicity to human fibroblasts in vitro and induced a sub-G1 peak in flow cytometry histogram of treated cells compared to the control. Western blot analysis demonstrated that EtOH and n-hexane extracts upregulated Bax expression, also it induced cleavage of PARP in HeLa cells compared to the control. In conclusion, L. angustifolia has cytotoxic and apoptotic effects in HeLa and MCF-7 cell lines, and apoptosis is proposed as the possible mechanism of action.


Assuntos
Apoptose/efeitos dos fármacos , Lavandula/química , Óleos Voláteis/farmacologia , Extratos Vegetais/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Ensaios de Seleção de Medicamentos Antitumorais , Fibroblastos/efeitos dos fármacos , Células HeLa/efeitos dos fármacos , Hexanos/química , Humanos , Células MCF-7/efeitos dos fármacos , Óleos Voláteis/química , Poli(ADP-Ribose) Polimerases/metabolismo , Proteína X Associada a bcl-2/metabolismo
16.
Toxicol Mech Methods ; 24(4): 307-14, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24593874

RESUMO

Breast and cervical cancers are the most common cancers in Iran and worldwide. Hormonal stimulation of cyclic adenosine mono phosphate (cAMP) and the cAMP-dependent protein kinase PKA regulates cell growth by different mechanism. cAMP can stimulate cell growth in many cell types while inhibiting cell growth in others. In some cell lines have been shown that the proliferation of tumor cells is reduced by increasing cAMP in cells. In this study, we evaluate growth arrest of selective PDE3 and non-selective PDE inhibitors, which lead to increase level of cAMP in cervical (HeLa) and breast cancer (MCF7) cell lines have been studied. Cells were incubated with different concentrations of selective, non-selective PDE inhibitors, beta adrenergic receptor agonist and direct stimulator of adenylyl cyclase. Cell viability was quantitated by MTT assay. Apoptotic cells were determined using PI staining of DNA fragmentation by flow cytometry (sub-G1 peak). Result showed that selective PDE inhibitors decreased cell viability in HeLa and MCF-7 cells as a time-dependent manner. Non-selective inhibitor and beta-adrenergic receptor agonist also decrease cell viability but they are less powerful than selective PDE3 inhibitors. Forskolin had no effect in viability of cells. Analysis of DNA fragmentation by flow cytometry showed apoptosis involved in selective PDE3 inhibitors induced toxicity in HeLa cell. Thus, the growth inhibitory effects of selective PDE3 inhibitors are more effective than non-selective inhibitor. Further studies are needed to investigate the mechanism of action is on the field.


Assuntos
Adenilil Ciclases/metabolismo , Proliferação de Células/efeitos dos fármacos , Ativadores de Enzimas/farmacologia , Inibidores da Fosfodiesterase 3/farmacologia , Apoptose/efeitos dos fármacos , Feminino , Células HeLa , Humanos , Células MCF-7
17.
Avicenna J Phytomed ; 14(3): 349-364, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39086858

RESUMO

Objective: The present work examined the anti-metastatic effects of auraptene and their underlying mechanisms of action in U87 Glioblastoma multiforme (GBM) cells. Materials and Methods: To test the hypothesis, cell culture, Matrigel invasion assay, scratch wound healing assay, gelatin zymography assay, qRT-PCR, and western blot experiments were conducted. Results: At sublethal concentrations of 12.5 and 25 µg/ml, auraptene exhibited a significant reduction in cell invasion and migration of U87 cells, as assessed using scratch wound healing and Transwell tests, respectively. The qRT-PCR and zymography experiments demonstrated a significant decrease in both mRNA expression and activities of MMP-2 and MMP-9 following auraptene treatment. Western blot analysis also showed that MMP-2 protein level and phosphorylation of metastasis-related proteins (p-JNK and p-mTOR) decreased in auraptene-treated cells. Molecular docking studies consistently demonstrated that auraptene exhibits a significant affinity towards MMP-2/-9, the ATP binding site of mTOR and JNK1/2/3. Conclusion: Auraptene inhibited the migration and invasion of GBM cells. This inhibitory effect was induced by modulating specific mechanisms, including suppressing MMPs, JNK, and mTOR activities.

18.
Physiol Rep ; 12(5): e15975, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38480374

RESUMO

Opium abuse and exposure to heavy metals elevate the risk of coronary artery disease (CAD). Therefore, we aimed to determine the association between opium abuse and blood lead levels (BLLs) and the CAD complexity. We evaluated patients with acute coronary symptoms who underwent coronary angiography, and those with >50% stenosis in at least one of the coronary arteries were included. Furthermore, Synergy between PCI with Taxus and Cardiac Surgery I (SYNTAX I) score and BLLs were measured. Based on the opium abuse, 95 patients were subdivided into opium (45) and control (50) groups. Differences in demographics and CAD risk factors were insignificant between the two groups. The median BLLs were remarkably higher in the opium group than in controls (36 (35.7) and 20.5 µg/dL (11.45), respectively, p = 0.003). We also revealed no significant differences in SYNTAX score between the two groups (15.0 (9.0) and 17.5 (14.0), respectively, p = 0.28). Additionally, we found no significant correlation between BLLs and the SYNTAX scores (p = 0.277 and r = -0.113). Opium abuse was associated with high BLLs. Neither opium abuse nor high BLLs were correlated with the complexity of CAD. Further studies are warranted to establish better the relationship between opium abuse, BLLs, and CAD.


Assuntos
Doença da Artéria Coronariana , Dependência de Ópio , Intervenção Coronária Percutânea , Humanos , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/etiologia , Chumbo/efeitos adversos , Dependência de Ópio/complicações , Dependência de Ópio/epidemiologia , Ópio/efeitos adversos , Índice de Gravidade de Doença
19.
IEEE Trans Nanobioscience ; 23(1): 118-126, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37379200

RESUMO

In this study, gold nanoparticles (Au-NPs) were synthesized using HAuCl4 and quince seed mucilage (QSM) extract, which was characterized by conventional methods including Fourier transforms electron microscopy (FTIR), UV-Visible spectroscopy (UV-Vis), Field emission electron microscopy (FESEM), Transmission electron microscopy (TEM), Dynamic light spectroscopy (DLS), and Zeta-potential. The QSM acted as reductant and stabilizing agents simultaneously. The NP's anticancer activity was also investigated against osteosarcoma cell lines (MG-63), which showed an IC50 of [Formula: see text]/mL.


Assuntos
Nanopartículas Metálicas , Neoplasias , Rosaceae , Humanos , Ouro/farmacologia , Ouro/química , Nanopartículas Metálicas/química , Células MCF-7 , Espectroscopia de Infravermelho com Transformada de Fourier
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