Dioscin inhibits human endometrial carcinoma proliferation via G0/G1 cell cycle arrest and mitochondrial-dependent signaling pathway

Xiao-Li Li; Run-Hui Ma; Zhi-Jing Ni; Kiran Thakur; Carlos L Cespedes-Acuña; Shaoyun Wang; Jian-Guo Zhang; Zhao-Jun Wei

doi:10.1016/j.fct.2020.111941

Dioscin inhibits human endometrial carcinoma proliferation via G0/G1 cell cycle arrest and mitochondrial-dependent signaling pathway

Food Chem Toxicol. 2021 Feb:148:111941. doi: 10.1016/j.fct.2020.111941. Epub 2020 Dec 24.

Authors

Xiao-Li Li¹, Run-Hui Ma², Zhi-Jing Ni³, Kiran Thakur⁴, Carlos L Cespedes-Acuña⁵, Shaoyun Wang⁶, Jian-Guo Zhang⁷, Zhao-Jun Wei⁸

Affiliations

¹ School of Food and Biological Engineering, Hefei University of Technology, Hefei, 230009, People's Republic of China. Electronic address: 15656561638@163.com.
² School of Food and Biological Engineering, Hefei University of Technology, Hefei, 230009, People's Republic of China; Collaborative Innovation Center for Food Production and Safety, School of Biological Science and Engineering, North Minzu University, Yinchuan, 750021, People's Republic of China. Electronic address: 1120355093@qq.com.
³ School of Food and Biological Engineering, Hefei University of Technology, Hefei, 230009, People's Republic of China; Collaborative Innovation Center for Food Production and Safety, School of Biological Science and Engineering, North Minzu University, Yinchuan, 750021, People's Republic of China. Electronic address: lovebear@vip.163.com.
⁴ School of Food and Biological Engineering, Hefei University of Technology, Hefei, 230009, People's Republic of China; Collaborative Innovation Center for Food Production and Safety, School of Biological Science and Engineering, North Minzu University, Yinchuan, 750021, People's Republic of China. Electronic address: kumarikiran@hfut.edu.cn.
⁵ Department of Basic Sciences, University of Bio-Bío, Andrés Bello Avenue, Chillan, Chile. Electronic address: ccespedes@ubiobio.cl.
⁶ College of Biological Science and Technology, Fuzhou University, Fuzhou, 350108, People's Republic of China. Electronic address: shywang@fzu.edu.cn.
⁷ School of Food and Biological Engineering, Hefei University of Technology, Hefei, 230009, People's Republic of China; Collaborative Innovation Center for Food Production and Safety, School of Biological Science and Engineering, North Minzu University, Yinchuan, 750021, People's Republic of China. Electronic address: zhangjianguo@hfut.edu.cn.
⁸ School of Food and Biological Engineering, Hefei University of Technology, Hefei, 230009, People's Republic of China; Collaborative Innovation Center for Food Production and Safety, School of Biological Science and Engineering, North Minzu University, Yinchuan, 750021, People's Republic of China. Electronic address: zjwei@hfut.edu.cn.

PMID: 33359023
DOI: 10.1016/j.fct.2020.111941

Abstract

The present study emphasized on the anti-cancerous effects of dioscin and its underlying molecular mechanism in human endometrial cancer Ishikawa cells. Dioscin significantly suppressed the proliferation of Ishikawa cells at IC₅₀ of 2.37 μM. Besides, dioscin could inhibit the proliferation of Ishikawa cells by blocking the G0/G1 cell cycle through up-regulation of p16, p21, and p27 and down-regulation of cycle-cellular protein (Cyclin A/D/E) and cyclin-dependent kinase (CDK2/4/6). Also, it promoted apoptosis through the mitochondrial pathway, including the regulation of Bcl family proteins, the increase of ROS levels, the activation of caspases (Caspase 9/3), and the decrease of mitochondrial membrane permeability. Whereas dioscin also effectively activated the marker genes and proteins (Fas, TNF-R1, and Caspase 8) related to the death receptor-mediated pathway which confirmed the involvement of both the pathways for dioscin-induced apoptosis. The current results demonstrated that dioscin possessed potential health benefits with respect to endometrial cancer prevention and treatment.

Keywords: Apoptosis; Cell cycle; Dioscin; Ishikawa; Mitochondrial pathway.

MeSH terms

Antineoplastic Agents / pharmacology*
Apoptosis / drug effects
Caspases / metabolism
Cell Line, Tumor
Cell Proliferation / drug effects*
Diosgenin / analogs & derivatives*
Diosgenin / pharmacology
Down-Regulation / drug effects
Drug Screening Assays, Antitumor
Endometrial Neoplasms / drug therapy*
Female
G1 Phase Cell Cycle Checkpoints / drug effects*
Gene Expression Regulation, Neoplastic / drug effects
Humans
Mitochondria / drug effects
Reactive Oxygen Species / metabolism
Signal Transduction / drug effects*
Up-Regulation / drug effects

Substances

Antineoplastic Agents
Reactive Oxygen Species
dioscin
Caspases
Diosgenin