Dioscin Induces Apoptosis in Human Cervical Carcinoma HeLa and SiHa Cells through ROS-Mediated DNA Damage and the Mitochondrial Signaling Pathway.

Xinwei Zhao,Xufeng Tao,Lina Xu,Jinyong Peng,Yan Qi,Xu Han,Youwei Xu,Lianhong Yin

doi:10.3390/molecules21060730

Abstract

Dioscin, a natural product, has activity against glioblastoma multiforme, lung cancer and colon cancer. In this study, the effects of dioscin against human cervical carcinoma HeLa and SiHa cells were further confirmed, and the possible mechanism(s) were investigated. A transmission electron microscopy (TEM) assay and DAPI staining were used to detect the cellular morphology. Flow cytometry was used to assay cell apoptosis, ROS and Ca2+ levels. Single cell gel electrophoresis and immunofluorescence assays were used to test DNA damage and cytochrome C release. The results showed that dioscin significantly inhibited cell proliferation and caused DNA damage in HeLa and SiHa cells. The mechanistic investigation showed that dioscin caused the release of cytochrome C from mitochondria into the cytosol. In addition, dioscin significantly up-regulated the protein levels of Bak, Bax, Bid, p53, caspase-3, caspase-9, and down-regulated the protein levels of Bcl-2 and Bcl-xl. Our work thus demonstrated that dioscin notably induces apoptosis in HeLa and SiHa cells through adjusting ROS-mediated DNA damage and the mitochondrial signaling pathway.

Highlights

Cervical carcinoma, a malignant gynecological disorder, is a common cause of death in females.The cervical cancer mortality rate ranks fourth among all kinds of cancers in China, and the second in gynecological cancers
Human papillomavirus (HPV) infection is the most important cause of cervical cancer, with more than 99% of cervical carcinomas testing positive for human HPV DNA [1]
SiHa cells waspresent significantly inhibited by dioscin in results a time- and dose-dependent

Summary

Introduction

A malignant gynecological disorder, is a common cause of death in females. The cervical cancer mortality rate ranks fourth among all kinds of cancers in China, and the second in gynecological cancers. Human papillomavirus (HPV) infection is the most important cause of cervical cancer, with more than 99% of cervical carcinomas testing positive for human HPV DNA [1]. The methods to treat cervical cancer mainly include surgery, radiotherapy and integrated Chinese and Western medicines. Cervical cancer is not sensitive to most cancer drugs, which results in low chemotherapy efficiency (

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