Your browser doesn't support javascript.
loading
10H-3,6-Diazaphenothiazine-Induced, Caspases-Mediated Mitochondrial-Dependent Apoptosis on HepG2 Hepatocellular Carcinoma Cells and Suppressed Cancer Cells Invasion via Inhibiting Mitochondrial Thioredoxin Reductase Enzymatic Activities.
Wang, Yuanxi; Gao, Feng; Ooi, Kah Kooi; Tai, Qinwen; Zhang, Jinhui; Zhu, Yiqiang; Kang, Junsheng; Zhong, Feng; Cai, Liquan; Fang, Fa; Ang, Kok Pian; Gao, Yi.
Afiliação
  • Wang Y; Department of General Surgery, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong Province, PR China; Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for A
  • Gao F; Department of General Surgery, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong Province, PR China.
  • Ooi KK; Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia.
  • Tai Q; Department of General Surgery, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong Province, PR China.
  • Zhang J; Department of General Surgery, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong Province, PR China.
  • Zhu Y; Department of General Surgery, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong Province, PR China.
  • Kang J; Department of General Surgery, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong Province, PR China.
  • Zhong F; Department of General Surgery, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong Province, PR China.
  • Cai L; Department of General Surgery, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong Province, PR China.
  • Fang F; Department of General Surgery, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong Province, PR China.
  • Ang KP; Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor, Malaysia.
  • Gao Y; Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou 510000
J Environ Pathol Toxicol Oncol ; 38(4): 297-311, 2019.
Article em En | MEDLINE | ID: mdl-32464002
Early development of liver cancer is usually asymptomatic. The overall survival rate of patients is relatively low due to late diagnosis, despite hepatocellular carcinoma being a common diagnosis. The high mortality rate of liver cancer was due to its overactivated cellular mitochondrial activities, namely thioredoxin reductase enzymatic activities and its downstream activation of nuclear factor kappa B (NF-κB) signaling pathways for cancer cell migration. Our previous study on this candidate compound on A2780 ovarian cancer cells and MCF-7 breast cancer cells, through modulation of cell-cycle checkpoints and respective targeted apoptosis pathways. The current study used HepG2 hepatocellular carcinoma cell lines as a representative in vitro liver cancer cell model. The half maximal inhibitory concentration (IC50) value was obtained via incubation of PTZ compound for 24 h yield of 37.03 µM, whereby it was three-fold more potent than the standard control tested, cisplatin (109.23 µM). The subsequent application of IC50 dosage of PTZ onto HepG2 cells illustrated a growth-static effect via activation of S-phase cell-cycle checkpoints, immediately followed by regulation of apoptosis. Increased cellular concentration of reactive oxygen species eventually generated oxidative damages on mitochondria, hence resulting in the release of cytochrome c protein and suppression of TrxR enzymatic activity, in conjunction with the suppression on invasion of cancer cells via Matrigel invasion chamber. In conclusion, PTZ was hypothesized to act effectively on mitochondria of HepG2 cells; hence it should proceed into detailed drug targeting mechanism research.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fenotiazinas / Tiorredoxina Dissulfeto Redutase / Apoptose / Neoplasias Hepáticas / Mitocôndrias Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fenotiazinas / Tiorredoxina Dissulfeto Redutase / Apoptose / Neoplasias Hepáticas / Mitocôndrias Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article