Dioscin Induces Apoptosis in Human Cervical Carcinoma HeLa and SiHa Cells through ROS-Mediated DNA Damage and the Mitochondrial Signaling Pathway.
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 Ca(2+) 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.
College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China. zhaoxinwei2015dy@163.com.
Xinwei
X
Zhao
College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China. taoxufeng@dmu.edu.cn.
Xufeng
X
Tao
College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China. Linaxu_632@126.com.
Lina
L
Xu
College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China. Lianhongyin_1980@163.com.
Lianhong
L
Yin
College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China. Yanqi_1976@163.com.
Yan
Y
Qi
College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China. Youweixu_1964@163.com.
Youwei
Y
Xu
College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China. Xuhan2002zs@163.com.
Xu
X
Han
College of Pharmacy, Dalian Medical University, Western 9 Lvshunnan Road, Dalian 116044, China. jinyongpeng2005@163.com.
Jinyong
J
Peng
D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects; D004144:Diosgenin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005260:Female; D006367:HeLa Cells; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000473:pathology
D017382:Reactive Oxygen Species; C019357:dioscin; D004144:Diosgenin
DNA damage; ROS; apoptosis; cervical carcinoma; dioscin