Roles of reactive oxygen species, mitochondrial membrane potential, and p53 in evodiamine-induced apoptosis and G2/M arrest of human anaplastic thyroid carcinoma cells

Chinese Medicine

Chih-Chiang Chien¹  Ming-Shun Wu²  Shih-Wei Chou³  Yen-Chou Chen⁴  Ganbolor Jargalsaikhan⁵ 

[1] Department of Nephrology, Chi-Mei Medical Center, Tainan, Taiwan;Department of Food Nutrition, Chung Hwa University of Medical Technology, Tainan, Taiwan;Division of Gastroenterology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan;Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan;Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, 250 Wu-Hsing St, 11031, Taipei, Taiwan;Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, 250 Wu-Hsing St, 11031, Taipei, Taiwan;International MS/PhD Program in Medicine, College of Medicine, Taipei Medical University, 11031, Taipei, Taiwan;Cancer Research Center and Orthopedics Research Center, Taipei Medical University Hospital, Taipei, Taiwan;Cell Physiology and Molecular Image Research Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan;International MS/PhD Program in Medicine, College of Medicine, Taipei Medical University, 11031, Taipei, Taiwan;Liver Center, 14230, Ulaanbaatar, Mongolia;

关键词: Anaplastic thyroid cancer (ATC);    Reactive oxygen species (ROS);    Mitochondria membrane potential (MMP);    Evodiamine (EVO);    Apoptosis;    G/M arrest;   

DOI  :  10.1186/s13020-021-00505-3

来源: Springer

【 摘 要 】

BackgroundOur previous studies have shown that evodiamine (EVO) as paclitaxel and nocodazole could trigger apoptosis in various human cancer cells including human renal cell carcinoma cells, colorectal carcinoma cells, and glioblastoma cells. This study aims to investigate the anti-cancer effects of EVO on human anaplastic thyroid carcinoma (ATC) cells, and underlining mechanism.MethodsTwo different endogenous p53 status human anaplastic thyroid carcinoma (ATC) cells including SW1736 (wtp53) and KAT4B (mutp53) were applied in the present study. The cytotoxicity of EVO on ATC cells was measured by MTT assay, and apoptosis and G2/M arrest were detected by propidium iodide (PI) staining followed by flow cytometry. Expression of indicated proteins was evaluated by Western blotting analysis, and pharmacological studies using chemical inhibitors and siRNA were performed for elucidating underlying mechanism. The roles of mitochondrial membrane potential and reactive oxygen species were investigated by flow cytometry using DiOC6 and DCFH-DA dye, respectively.ResultsSW1736 (wtp53) cells showed a higher apoptotic percentage than KAT4B (mutp53) cells in response to EVO stimulation via a flow cytometric analysis. Mechanistic studies showed that increased p53 and its downstream proteins, and disrupted MMP with increased intracellular peroxide production participated in EVO-induced apoptosis and G2/M arrest of SW1736 cells. In EVO-treated KAT4B cells, significant increases in G2/M percentage but little apoptotic events by EVO was observed. Structure-activity analysis showed that an alkyl group at position 14 was critical for induction of apoptosis related to ROS production and MMP disruption in SW1736 cells.ConclusionEvidence indicated that the endogenous p53 status affected the sensitivity of ATC cells to EVO-induced apoptosis and G2/M arrest, revealing the potential role of p53 related to increased ROS production and disrupted MMP in the anticancer actions of EVO, and alkylation at position 14 of EVO is a critical substitution for apoptosis of ATC cells.

【 授权许可】

CC BY