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1.
Curr Issues Mol Biol ; 46(2): 1621-1634, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38392223

RESUMO

Docetaxel (DTX), a semi-synthetic analogue of paclitaxel (taxol), is known to exert potent anticancer activity in various cancer cells by suppressing normal microtubule dynamics. In this study, we examined how the anticancer effect of DTX is regulated by polyphenols extracted from Korean Artemisia annua L. (pKAL) in DU145 prostate cancer cells (mutant p53) and HCT116 colorectal cancer cells (wild-type p53). Here, we show that the anticancer effect of DTX was enhanced more significantly by pKAL in HCT116 cells than in DU145 cells via phase-contrast microscopy, CCK-8 assay, Western blot, and flow cytometric analysis of annexin V/propidium iodide-stained cells. Notably, mutant p53 was slightly downregulated by single treatment of pKAL or DTX in DU145 cells, whereas wild-type p53 was significantly upregulated by pKAL or DTX in HCT116 cells. Moreover, the enhanced anticancer effect of DTX by pKAL in HCT116 cells was significantly associated with the suppression of DTX-induced p53 upregulation, increase of DTX-induced phospho-p38, and decrease of DTX-regulated cyclin A, cyclin B1, AKT, caspase-8, PARP1, GM130, NF-κB p65, and LDHA, leading to the increased apoptotic cell death and plasma membrane permeability. Our results suggest that pKAL could effectively improve the anticancer effect of DTX-containing chemotherapy used to treat various cancers expressing wild-type p53.

2.
Int J Mol Sci ; 24(24)2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38139333

RESUMO

Recent studies suggest that the anticancer activity of ß-lapachone (ß-Lap) could be improved by different types of bioactive phytochemicals. The aim of this study was to elucidate how the anticancer effect of ß-Lap is regulated by polyphenols extracted from Korean Artemisia annua L. (pKAL) in parental HCT116 and oxaliplatin-resistant (OxPt-R) HCT116 colorectal cancer cells. Here, we show that the anticancer effect of ß-Lap is more enhanced by pKAL in HCT116-OxPt-R cells than in HCT116 cells via a CCK-8 assay, Western blot, and phase-contrast microscopy analysis of hematoxylin-stained cells. This phenomenon was associated with the suppression of OxPt-R-related upregulated proteins including p53 and ß-catenin, the downregulation of cell survival proteins including TERT, CD44, and EGFR, and the upregulation of cleaved HSP90, γ-H2AX, and LC3B-I/II. A bioinformatics analysis of 21 proteins regulated by combined treatment of pKAL and ß-Lap in HCT116-OxPt-R cells showed that the enhanced anticancer effect of ß-Lap by pKAL was related to the inhibition of negative regulation of apoptotic process and the induction of DNA damage through TERT, CD44, and EGFR-mediated multiple signaling networks. Our results suggest that the combination of pKAL and ß-Lap could be used as a new therapy with low toxicity to overcome the OxPt-R that occurred in various OxPt-containing cancer treatments.


Assuntos
Antineoplásicos , Artemisia annua , Neoplasias Colorretais , Humanos , Oxaliplatina/farmacologia , Células HCT116 , Polifenóis/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Receptores ErbB , Linhagem Celular Tumoral , Antineoplásicos/farmacologia
3.
Int J Mol Sci ; 24(12)2023 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-37373014

RESUMO

ß-lapachone (ß-Lap), a topoisomerase inhibitor, is a naturally occurring ortho-naphthoquinone phytochemical and is involved in drug resistance mechanisms. Oxaliplatin (OxPt) is a commonly used chemotherapeutic drug for metastatic colorectal cancer, and OxPt-induced drug resistance remains to be solved to increase chances of successful therapy. To reveal the novel role of ß-Lap associated with OxPt resistance, 5 µM OxPt-resistant HCT116 cells (HCT116-OxPt-R) were generated and characterized via hematoxylin staining, a CCK-8 assay and Western blot analysis. HCT116-OxPt-R cells were shown to have OxPt-specific resistance, increased aggresomes, upregulated p53 and downregulated caspase-9 and XIAP. Through signaling explorer antibody array, nucleophosmin (NPM), CD37, Nkx-2.5, SOD1, H2B, calreticulin, p38 MAPK, caspase-2, cadherin-9, MMP23B, ACOT2, Lys-acetylated proteins, COL3A1, TrkA, MPS-1, CD44, ITGA5, claudin-3, parkin and ACTG2 were identified as OxPt-R-related proteins due to a more than two-fold alteration in protein status. Gene ontology analysis suggested that TrkA, Nkx-2.5 and SOD1 were related to certain aggresomes produced in HCT116-OxPt-R cells. Moreover, ß-Lap exerted more cytotoxicity and morphological changes in HCT116-OxPt-R cells than in HCT116 cells through the downregulation of p53, Lys-acetylated proteins, TrkA, p38 MAPK, SOD1, caspase-2, CD44 and NPM. Our results indicate that ß-Lap could be used as an alternative drug to overcome the upregulated p53-containing OxPt-R caused by various OxPt-containing chemotherapies.


Assuntos
Neoplasias Colorretais , Proteína Supressora de Tumor p53 , Humanos , Oxaliplatina/farmacologia , Oxaliplatina/uso terapêutico , Células HCT116 , Proteína Supressora de Tumor p53/metabolismo , Superóxido Dismutase-1/metabolismo , Neoplasias Colorretais/patologia , Caspase 2/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Nucleofosmina , Receptores Proteína Tirosina Quinases/metabolismo , Apoptose , Linhagem Celular Tumoral , Receptores de Hialuronatos/metabolismo
4.
Healthcare (Basel) ; 10(3)2022 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-35327048

RESUMO

Pelvic floor muscle training (PFMT) has been recommended as the first choice as one of the effective methods for preventing and improving urinary incontinence (UI). We aimed to determine whether pressure biofeedback unit training (PBUT) improves short term and retention performance of pelvic floor muscle contraction. The muscle activities of the external oblique (EO), transversus/internal oblique (TrA/IO), multifidus (MF) and the bladder base displacement were measured in the verbal feedback group (n = 10) and PBU group (n = 10) three times (baseline, post-training, and at the 1-week follow-up). Surface electromyographic activity was recorded from the EO, TrA/IO, and MF muscles. The bladder base displacement was measured using ultrasound. The results were analyzed using two way mixed ANOVA. The bladder base displacement may have elevated more in the PBU group than in the verbal feedback group due to decreased TrA/IO activity. These findings indicate that PBUT is a better method than verbal feedback training.

5.
Int J Mol Sci ; 23(3)2022 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-35163520

RESUMO

The anticancer effects of natural phytochemicals are relevant to the modulation of cytokine signaling pathways in various cancer cells with stem-like properties as well as immune cells. The aim of this study was to elucidate a novel anticancer mechanism of Artemisia annua L. polyphenols (pKAL) involved in the regulation of growth factors, cytokines and mediators in stem-like HCT116 colorectal cancer cells. Through RayBiotech human L-1000 antibody array and bioinformatics analysis, we show here that pKAL-induced anticancer effects are associated with downregulation of growth factor and cytokine signaling proteins including TGFA, FGF16, PDGFC, CCL28, CXCR3, IRF6 and SMAD1. Notably, we found that TGF-ß signaling proteins such as GDF10, ENG and TGFBR2 and well-known survival proteins such as NGF-ß, VEGFD and insulin were significantly upregulated by pKAL. Moreover, the results of hematoxylin staining, cell viability assay and Western blot analysis demonstrated that TGF-ß1 and NGF-ß attenuated pKAL-induced anticancer effects by inhibiting pKAL-induced downregulation of caspase-8, NF-κB p65 and cyclin D1. These results suggest that certain survival mediators may be activated by pKAL through the TGF-ß1 and NGF-ß signaling pathways during pKAL-induced cell death and thus, strategies to inhibit the survival signaling are inevitably required for more effective anticancer effects of pKAL.


Assuntos
Artemisia annua/química , Neoplasias Colorretais/metabolismo , Fator de Crescimento Neural/metabolismo , Polifenóis/farmacologia , Fator de Transcrição RelA/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HCT116 , Humanos , Insulina/metabolismo , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Polifenóis/química , Análise Serial de Proteínas
6.
Healthcare (Basel) ; 11(1)2022 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-36611520

RESUMO

Pilates methods use mats for trunk muscles stabilization exercises, and leg pull front (LPF) is one of the traditional Pilates mat exercises. Abdominal hollowing (AH) and Abdominal bracing (AB) maneuvers are recommended to stabilize the trunk muscles and prevent unwanted pelvic movement during motion. This study aimed to explore the effects of AH and AB on electromyography (EMG) activity of the trunk muscles and angle of pelvic rotation during LPF. A total of 20 healthy volunteers participated in the study. AH, AB, and without any condition (WC) were randomly performed during LPF exercise. Each was repeated three times for 5 s. The trunk muscle activities were measured using EMG and rotation of pelvis was measured using a Smart KEMA device. The activities of the transversus abdominis/obliquus internus abdominis (TrA/IO) and right obliquus externus abdominis (EO) muscles were highest in LPF-AH compared to the other conditions. Multifidus (MF) activity was significantly greater in LPF-AH and LPF-AB compared to that of without any condition. The pelvic rotation angle was significantly smaller in LPF-AB. Therefore, AH maneuver during LPF for trunk muscle stabilization exercises is suitable for selective activation of the TrA/IO, and AB maneuver during LPF is recommended for the prevention of unwanted pelvic rotation.

7.
Int J Mol Sci ; 22(22)2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34830320

RESUMO

Emerging evidence suggests that breast cancer stem cells (BCSCs), and epithelial-mesenchymal transition (EMT) may be involved in resistance to doxorubicin. However, it is unlear whether the doxorubicin-induced EMT and expansion of BCSCs is related to cancer dormancy, or outgrowing cancer cells with maintaining resistance to doxorubicin, or whether the phenotypes can be transferred to other doxorubicin-sensitive cells. Here, we characterized the phenotype of doxorubicin-resistant TNBC cells while monitoring the EMT process and expansion of CSCs during the establishment of doxorubicin-resistant MDA-MB-231 human breast cancer cells (DRM cells). In addition, we assessed the potential signaling associated with the EMT process and expansion of CSCs in doxorubicin-resistance of DRM cells. DRM cells exhibited morphological changes from spindle-shaped MDA-MB-231 cells into round-shaped giant cells. They exhibited highly proliferative, EMT, adhesive, and invasive phenotypes. Molecularly, they showed up-regulation of Cyclin D1, mesenchymal markers (ß-catenin, and N-cadherin), MMP-2, MMP-9, ICAM-1 and down-regulation of E-cadherin. As the molecular mechanisms responsible for the resistance to doxorubicin, up-regulation of EGFR and its downstream signaling, were suggested. AKT and ERK1/2 expression were also increased in DRM cells with the advancement of resistance to doxorubicin. Furthermore, doxorubicin resistance of DRM cells can be transferred by autocrine signaling. In conclusion, DRM cells harbored EMT features with CSC properties possessing increased proliferation, invasion, migration, and adhesion ability. The doxorubicin resistance, and doxorubicin-induced EMT and CSC properties of DRM cells, can be transferred to parental cells through autocrine signaling. Lastly, this feature of DRM cells might be associated with the up-regulation of EGFR.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Comunicação Autócrina/efeitos dos fármacos , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Células-Tronco Neoplásicas/efeitos dos fármacos , Antígenos CD/genética , Antígenos CD/metabolismo , Comunicação Autócrina/genética , Caderinas/genética , Caderinas/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ciclina D1/genética , Ciclina D1/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Transição Epitelial-Mesenquimal/genética , Receptores ErbB/genética , Receptores ErbB/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Molécula 1 de Adesão Intercelular/genética , Molécula 1 de Adesão Intercelular/metabolismo , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , beta Catenina/genética , beta Catenina/metabolismo
8.
Int J Syst Evol Microbiol ; 71(10)2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34596509

RESUMO

A bacterial strain, designated TCH3-2T, was isolated from the rhizosphere of tomato plant grown at Dong-A University Agricultural Experiment Station, Republic of Korea. The strain was Gram-stain-negative, obligate aerobic, orange yellow-coloured, motile by gliding and short rod-shaped. Strain TCH3-2 T only grew on 1/2 tryptic soy agar and Luria-Bertani agar among the media tested, with optimum growth at 28 °C and pH 7. Salt of 1 % NaCl was necessary to support the growth of TCH3-2T. Strain TCH3-2T produced flexirubin-type pigments. The predominant cellular fatty acids were iso-C15 : 0 (55.6 %), iso-C17 : 0 3-OH (17.9 %), summed feature 9 (comprising C16 : 0 10-methyl and/or iso-C17 : 1 ω9c; 10.5 %), iso-C15 : 0 3-OH (4.8 %) and anteiso-C15 : 0 (2.3 %). The major menaquinone was menaquinone-6 and the major polar lipids were phosphatidylethanolamine, five unknown aminolipids and three unknown lipids. Phylogenetic analysis based on 16S rRNA sequences indicated that TCH3-2T was closely related to Flavobacterium ummariense DS-12T (95.16 %), Flavobacterium marinum SW105T (95.14 %) and Flavobacterium viscosus YIM 102796T (94.54 %). The draft genome of TCH3-2T comprised ca. 2.8 Mb with a G+C content of 34.61 mol%. The average nucleotide identity and digital DNA-DNA hybridization values between TCH3-2T and closely related Flavobacterium species showed that it belongs to a distinct species. Furthermore, the results of morphological, physiological and biochemical tests allowed further phenotypic differentiation of TCH3-2T from its closest relatives. Thus, chemotaxonomic characteristics together with phylogenetic affiliation illustrate that TCH3-2T represents a novel species of the genus Flavobacterium, for which the name Flavobacterium dauae sp. nov. (type strain TCH3-2T=KACC 19054T=JCM 34025T) is proposed.


Assuntos
Flavobacterium , Filogenia , Rizosfera , Microbiologia do Solo , Solanum lycopersicum , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Ácidos Graxos/química , Flavobacterium/classificação , Flavobacterium/isolamento & purificação , Solanum lycopersicum/microbiologia , Hibridização de Ácido Nucleico , Fosfolipídeos/química , Pigmentação , RNA Ribossômico 16S/genética , República da Coreia , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/química
9.
Int J Mol Sci ; 22(9)2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-34066541

RESUMO

Breast cancer is one of the major causes of deaths due to cancer, especially in women. The crucial barrier for breast cancer treatment is resistance to radiation therapy, one of the important local regional therapies. We previously established and characterized radio-resistant MDA-MB-231 breast cancer cells (RT-R-MDA-MB-231 cells) that harbor a high expression of cancer stem cells (CSCs) and the EMT phenotype. In this study, we performed antibody array analysis to identify the hub signaling mechanism for the radiation resistance of RT-R-MDA-MB-231 cells by comparing parental MDA-MB-231 (p-MDA-MB-231) and RT-R-MDA-MB-231 cells. Antibody array analysis unveiled that the MAPK1 protein was the most upregulated protein in RT-R-MDA-MB-231 cells compared to in p-MDA-MB-231 cells. The pathway enrichment analysis also revealed the presence of MAPK1 in almost all enriched pathways. Thus, we used an MEK/ERK inhibitor, PD98059, to block the MEK/ERK pathway and to identify the role of MAPK1 in the radio-resistance of RT-R-MDA-MB-231 cells. MEK/ERK inhibition induced cell death in both p-MDA-MB-231 and RT-R-MDA-MB-231 cells, but the death mechanism for each cell was different; p-MDA-MB-231 cells underwent apoptosis, showing cell shrinkage and PARP-1 cleavage, while RT-R-MDA-MB-231 cells underwent necroptosis, showing mitochondrial dissipation, nuclear swelling, and an increase in the expressions of CypA and AIF. In addition, MEK/ERK inhibition reversed the radio-resistance of RT-R-MDA-MB-231 cells and suppressed the increased expression of CSC markers (CD44 and OCT3/4) and the EMT phenotype (ß-catenin and N-cadherin/E-cadherin). Taken together, this study suggests that activated ERK signaling is one of the major hub signals related to the radio-resistance of MDA-MB-231 breast cancer cells.


Assuntos
Neoplasias da Mama/enzimologia , Neoplasias da Mama/radioterapia , Sistema de Sinalização das MAP Quinases , Tolerância a Radiação , Apoptose/efeitos dos fármacos , Fator de Indução de Apoptose/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Forma Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Clonais , Ciclofilina A/metabolismo , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Feminino , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Necroptose/efeitos dos fármacos , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Fenótipo , Poli(ADP-Ribose) Polimerases/metabolismo , Mapas de Interação de Proteínas/efeitos dos fármacos , Inibidores de Proteínas Quinases/farmacologia , Proteômica , Tolerância a Radiação/efeitos dos fármacos
10.
Ann Surg Treat Res ; 100(5): 298-304, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34012948

RESUMO

PURPOSE: The aim of this study is to investigate the effect of the surgical hospitalist system on postoperative outcomes and hospital costs for surgical patients. METHODS: We reviewed the medical records of 522 patients who were admitted to the divisions of colorectal and gastrointestinal surgery for operation from September to December 2017 at Severance Hospital, Yonsei University College of Medicine in Seoul, Korea. All patients were divided into 2 groups; one that was managed by surgical hospitalists group (HG) and another that was managed by non-hospitalist residents group (NHG) after elective surgery. Postoperative outcomes and hospital costs were analyzed for each group. RESULTS: Two hundred ninety-eight patients were managed by HG and 189 patients were managed by NHG after surgery. The length of hospital stay in the first group was shorter (9.6 ± 5.8 days vs. 12.2 ± 7.9 days, P < 0.001), the incidence of complications was lower (44.6% vs. 55.6%, P = 0.019), and the readmission rate was lower (3.0% vs. 6.9%, P = 0.046) in the HG than in the NHG. The difference in total hospital costs was not significant between the HG and the NHG (₩8,381,304 vs. ₩9,242,493, P = 0.559), but surgery-independent hospital costs were lower in the HG than in the NHG (₩3,020,873 vs. ₩3,923,308, P = 0.001). CONCLUSION: The surgical hospitalist system reduced the length of hospital stay, the incidence of postoperative complications, and the readmission rates of surgical patients. This led to the effect of a reduction in total hospital costs.

11.
Int J Mol Sci ; 22(3)2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33573023

RESUMO

c-Jun N-terminal kinase (JNK) is activated by chemotherapeutic reagents including natural plant polyphenols, and cell fate is determined by activated phospho-JNK as survival or death depending on stimuli and cell types. The purpose of this study was to elucidate the role of JNK on the anticancer effects of the Korean plant Artemisia annua L. (pKAL) polyphenols in p53 wild-type HCT116 human colorectal cancer cells. Cell morphology, protein expression levels, apoptosis/necrosis, reactive oxygen species (ROS), acidic vesicles, and granularity/DNA content were analyzed by phase-contrast microscopy; Western blot; and flow cytometry of annexin V/propidium iodide (PI)-, dichlorofluorescein (DCF)-, acridine orange (AO)-, and side scatter pulse height (SSC-H)/DNA content (PI)-stained cells. The results showed that pKAL induced morphological changes and necrosis or late apoptosis, which were associated with loss of plasma membrane/Golgi integrity, increased acidic vesicles and intracellular granularity, and decreased DNA content through downregulation of protein kinase B (Akt)/ß-catenin/cyclophilin A/Golgi matrix protein 130 (GM130) and upregulation of phosphorylation of H2AX at Ser-139 (γ-H2AX)/p53/p21/Bak cleavage/phospho-JNK/p62/microtubule-associated protein 1 light chain 3B (LC3B)-I. Moreover, JNK inhibition by SP600125 enhanced ROS-independently pKAL-induced cell death through downregulation of p62 and upregulation of p53/p21/Bak cleavage despite a reduced state of DNA damage marker γ-H2AX. These findings indicate that phospho-JNK activated by pKAL inhibits p53-dependent cell death signaling and enhances DNA damage signaling, but cell fate is determined by phospho-JNK as survival rather than death in p53 wild-type HCT116 cells.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Artemisia annua , Neoplasias Colorretais/tratamento farmacológico , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Polifenóis/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Antineoplásicos Fitogênicos/química , Artemisia annua/química , Morte Celular/efeitos dos fármacos , Neoplasias Colorretais/metabolismo , Células HCT116 , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Polifenóis/química , Inibidores de Proteínas Quinases/química , Espécies Reativas de Oxigênio/metabolismo
12.
Int J Mol Sci ; 21(23)2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33297377

RESUMO

Plant-derived natural polyphenols exhibit anticancer activity without showing any noticeable toxicities to normal cells. The aim of this study was to investigate the role of p53 on the anticancer effect of polyphenols isolated from Korean Artemisia annua L. (pKAL) in HCT116 human colorectal cancer cells. We confirmed that pKAL induced reactive oxygen species (ROS) production, propidium iodide (PI) uptake, nuclear structure change, and acidic vesicles in a p53-independent manner in p53-null HCT116 cells through fluorescence microscopy analysis of DCF/PI-, DAPI-, and AO-stained cells. The pKAL-induced anticancer effects were found to be significantly higher in p53-wild HCT116 cells than in p53-null by hematoxylin staining, CCK-8 assay, Western blot, and flow cytometric analysis of annexin V/PI-stained cells. In addition, expression of ectopic p53 in p53-null cells was upregulated by pKAL in both the nucleus and cytoplasm, increasing pKAL-induced cell death. Moreover, Western bot analysis revealed that pKAL-induced cell death was associated with upregulation of p53-dependent targets such as p21, Bax and DR5 and cleavage of PARP1 and lamin A/C in p53-wild HCT116 cells, but not in p53-null. Taken together, these results indicate that p53 plays an important role in enhancing the anticancer effects of pKAL by upregulating p53 downstream targets and inducing intracellular cell death processes.


Assuntos
Antineoplásicos/toxicidade , Morte Celular , Polifenóis/toxicidade , Proteína Supressora de Tumor p53/metabolismo , Artemisia annua/química , Células HCT116 , Humanos , Laminas/metabolismo , Poli(ADP-Ribose) Polimerase-1/metabolismo , Proteólise , Regulação para Cima
13.
Molecules ; 25(16)2020 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-32784919

RESUMO

Anthocyanins isolated from Vitis coignetiae Pulliat (Meoru in Korea) (AIMs) have various anti-cancer properties by inhibiting Akt and NF-κB which are involved in drug resistance. Cisplatin (CDDP) is one of the popular anti-cancer agents. Studies reported that MCF-7 human breast cancer cells have high resistance to CDDP compared to other breast cancer cell lines. In this study, we confirmed CDDP resistance of MCF-7 cells and tested whether AIMs can overcome CDDP resistance of MCF-7 cells. Cell viability assay revealed that MCF-7 cells were more resistant to CDDP treatment than MDA-MB-231 breast cancer cells exhibiting aggressive and high cancer stem cell phenotype. AIMs significantly augmented the efficacy of CDDP with synergistic effects on MCF-7 cells. Molecularly, Western blot analysis revealed that CDDP strongly increased Akt and moderately reduced p-NF-κB and p-IκB and that AIMs inhibited CDDP-induced Akt activation, and augmented CDDP-induced reduction of p-NF-κB and p-IκB in MCF-7 cells. In addition, AIMs significantly downregulated an anti-apoptotic protein, XIAP, and augmented PARP-1 cleavage in CDDP-treated MCF-7 cells. Moreover, under TNF-α treatment, AIMs augmented CDDP efficacy with inhibition of NF-κB activation on MCF-7 cells. In conclusion, AIMs enhanced CDDP sensitivity by inhibiting Akt and NF-κB activity of MCF-7 cells that show relative intrinsic CDDP resistance.


Assuntos
Antocianinas/farmacologia , Neoplasias da Mama/tratamento farmacológico , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos , NF-kappa B/metabolismo , Extratos Vegetais/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Vitis/química , Antineoplásicos/farmacologia , Apoptose , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Ciclo Celular , Movimento Celular , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , NF-kappa B/genética , Proteínas Proto-Oncogênicas c-akt/genética , Células Tumorais Cultivadas
14.
Molecules ; 25(10)2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32455624

RESUMO

Vitis coignetiae Pulliat (Meoru in Korea) has been used in Korean folk medicine for the treatment of inflammatory diseases and cancers. Evidence suggests that NF-κB activation is mainly involved in cancer cell proliferation, invasion, angiogenesis, and metastasis. TNF-α also enhances the inflammatory process in tumor development. Recently, flavonoids from plants have been reported to have inhibitory effects on NF-κB activities. We investigated the effects of anthocyanins extracted from the fruits of Vitis coignetiae Pulliat (AIM, anthocyanins isolated from Meoru (AIM)) on TNF-α-induced NF-κB activities in MCF-7 human breast cancer cells and the molecules involved in AIM-induced anti-cancer effects, especially on cancer metastasis. We performed cell viability assay, gelatin zymography, invasion assay, and western blot analysis to unravel the anti-NF-κB activity of AIMs on MCF-7 cells. AIM suppressed the TNF-α effects on the NF-κB-regulated proteins involved in cancer cell proliferation (COX-2, C-myc), invasion, and angiogenesis (MMP-2, MMP9, ICAM-1, and VEGF). AIM also increased the expression of E-cadherin, which is one of the hallmarks of the epithelial-mesenchymal transition (EMT) process. In conclusion, this study demonstrates that the anthocyanins isolated from the fruits of Vitis coignetiae Pulliat acts as an inhibitor of TNF-α induced NF-κB activation, and subsequent downstream molecules involved in cancer proliferation, invasion, adhesion, angiogenesis, and thus have anti-metastatic activities in MCF-7 breast cancer cells.


Assuntos
Antocianinas/farmacologia , Neoplasias da Mama/tratamento farmacológico , Fator de Necrose Tumoral alfa/genética , Vitis/química , Antocianinas/química , Antocianinas/isolamento & purificação , Apoptose/efeitos dos fármacos , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Feminino , Frutas/química , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Células MCF-7 , NF-kappa B/genética , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Proteínas de Neoplasias/genética
15.
Molecules ; 25(8)2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32326231

RESUMO

Artemisia annua L. has been reported to show anti-cancer activities. Here, we determined whether polyphenols extracted from Artemisia annua L. (pKAL) exhibit anti-cancer effects on radio-resistant MDA-MB-231 human breast cancer cells (RT-R-MDA-MB-231 cells), and further explored their molecular mechanisms. Cell viability assay and colony-forming assay revealed that pKAL inhibited cell proliferation on both parental and RT-R-MDA-MB-231 cells in a dose-dependent manner. The anti-proliferative effects of pKAL on RT-R-MDA-MB-231 cells were superior or similar to those on parental ones. Western blot analysis revealed that expressions of cluster of differentiation 44 (CD44) and Oct 3/4, matrix metalloproteinase-9 (MMP-9) and signal transducer and activator of transcription-3 (STAT-3) phosphorylation were significantly increased in RT-R-MDA-MB-231 cells compared to parental ones, suggesting that these proteins could be associated with RT resistance. pKAL inhibited the expression of CD44 and Oct 3/4 (CSC markers), and ß-catenin and MMP-9 as well as STAT-3 phosphorylation of RT-R-MDA-MB-231. Regarding upstream signaling, the JNK or JAK2 inhibitor could inhibit STAT-3 activation in RT-R-MDA-MB-231 cells, but not augmented pKAL-induced anti-cancer effects. These findings suggest that c-Jun N-terminal kinase (JNK) or Janus kinase 2 (JAK2)/STAT3 signaling are not closely related to the anti-cancer effects of pKAL. In conclusion, this study suggests that pKAL exhibit anti-cancer effects on RT-R-MDA-MB-231 cells by suppressing CD44 and Oct 3/4, ß-catenin and MMP-9, which appeared to be linked to RT resistance of RT-R-MDA-MB-231 cells.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Artemisia annua/química , Metaloproteinase 9 da Matriz/metabolismo , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Extratos Vegetais/farmacologia , Polifenóis/farmacologia , beta Catenina/metabolismo , Antineoplásicos Fitogênicos/química , Biomarcadores , Biomarcadores Tumorais , Neoplasias da Mama , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Expressão Gênica , Humanos , Imunofenotipagem , Janus Quinase 2/metabolismo , Extratos Vegetais/química , Polifenóis/química , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos
16.
Arch Gerontol Geriatr ; 83: 179-184, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31071534

RESUMO

INTRODUCTION: This study aimed to assess the health benefits of a geriatric screening program comprising of physical function tests, screening questionnaires for depression and cognitive impairment, and bone mineral density measurements for women as a part of the National Screening Program for Transitional Ages (NSPTA). We compared the all-cause mortality between subjects who did and did not participate in the screening program. METHODS: This was a nationwide longitudinal study with a 5-year follow-up based on a 10% sample of the National Health Insurance beneficiaries aged 60 years and older. Mortality records were obtained from the qualification dataset in the elderly cohort database of 2005-2013 provided by the National Health Insurance Service. A Cox proportional hazards model was used to analyze the mortality risk. We sampled 11,986 subjects each in the screened (intervention) and non-screened (control) groups after exact matching using propensity score. RESULTS: After adjusting for demographic and socioeconomic characteristics (age, sex, household income, smoking, alcohol drinking, physical activity, body mass index, and the Charlson Comorbidity Index), all-cause mortality rates were found to be significantly lower (a) in the intervention group compared to the control group (hazard ratio = 0.73; 95% confidence interval: 0.65, 0.82) and (b) among women compared to men (hazard ratio = 0.50; 95% confidence interval: 0.44, 0.56). Lower hazard ratios were also observed among those with a higher body mass index, fewer comorbidities, and higher income. CONCLUSION: A nationwide geriatric screening program might be helpful in reducing the incidence of premature deaths among older people.


Assuntos
Avaliação Geriátrica , Taxa de Sobrevida , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Estudos de Coortes , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Programas Nacionais de Saúde , República da Coreia/epidemiologia
18.
Nat Biotechnol ; 2018 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-30295674

RESUMO

Tomato variety Hawaii 7996 is resistant to the soil-borne pathogen Ralstonia solanacearum, whereas the Moneymaker variety is susceptible to the pathogen. To evaluate whether plant-associated microorganisms have a role in disease resistance, we analyzed the rhizosphere microbiomes of both varieties in a mesocosm experiment. Microbiome structures differed between the two cultivars. Transplantation of rhizosphere microbiota from resistant plants suppressed disease symptoms in susceptible plants. Comparative analyses of rhizosphere metagenomes from resistant and susceptible plants enabled the identification and assembly of a flavobacterial genome that was far more abundant in the resistant plant rhizosphere microbiome than in that of the susceptible plant. We cultivated this flavobacterium, named TRM1, and found that it could suppress R. solanacearum-disease development in a susceptible plant in pot experiments. Our findings reveal a role for native microbiota in protecting plants from microbial pathogens, and our approach charts a path toward the development of probiotics to ameliorate plant diseases.

19.
J Phys Ther Sci ; 30(4): 504-506, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29706695

RESUMO

[Purpose] This study was to investigate differences in the level of activity of the external oblique (EO), internal oblique (IO), and multifidus (MF) muscles with deep breathing in three sitting postures. [Subjects and Methods] Sixteen healthy women were recruited. The muscle activity (EO, IO, MF) of all subjects was measured in three sitting postures (slumped, thoracic upright, and lumbo-pelvic upright sitting postures) using surface electromyography. The activity of the same muscles was then remeasured in the three sitting postures during deep breathing. [Results] Deep breathing significantly increased activity in the EO, IO, and MF compared with normal breathing. Comparing postures, the activity of the MF and IO muscles was highest in the lumbo-pelvic upright sitting posture. [Conclusion] An lumbo-pelvic upright sitting posture with deep breathing could increase IO and MF muscle activity, thus improving lumbo-pelvic region stability.

20.
Ann Surg Treat Res ; 94(1): 13-18, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29333421

RESUMO

PURPOSE: The detection rate of brain metastasis (BM) from colorectal cancer (CRC) is increasing. This study was designed to analyze the clinical features of BM and prognosis according to the therapeutic modalities. METHODS: A total of 19 cases were collected in this study between November 2008 and December 2015. We reviewed the patients' demographic data and the clinical features of BM retrospectively and investigated their prognostic significance. RESULTS: Nineteen patients included 8 male and 11 female patients. The median age at diagnosis of BM was 62.4 years (range, 32-83 years). The median interval between diagnosis of CRC and BM was 39 months (range, 0-98 months). Eighteen patients (94.7%) had extracranial metastasis at the diagnosis of BM. Lung was the most common site of extracranial metastasis in 14 patients (73.7%). Synchronous BMs were found at the diagnosis of primary CRC in 2 patients (10.5%). The location of primary CRC was the colon in 6 patients (31.6%) and the rectum in 13 patients (68.4%). At the diagnosis of BM, 10 patients (52.6%) had a solitary BM. The common neurologic symptoms were headache in 8 cases (42.1%) and ataxia in 6 cases (31.6%). The median survival after the diagnosis of BM was 3 months (range, 1-10 months). The patients who underwent surgery plus stereotactic radiosurgery (SRS) had an improved survival (range, 3-10 months) than the other patients (range, 1-6 months) (P = 0.016). CONCLUSION: In patients with BM from CRC, surgical resection plus SRS might improve survival.

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