Aesculetin-induced apoptosis through a ROS-mediated mitochondrial dysfunction pathway in human cervical cancer cells.
Aesculetin (1) is an important coumarin found in various plant materials. It has been shown to have antiproliferative effects on several types of human cancer cells, but its effect on cervical cancer cells in vitro is unknown. In this study, we investigated that the cytotoxic effect of 1 on a non-cancer cell line (293) was smaller than on a tumor cell line (HeLa). This is the first report showing the possible mechanism of antiproliferative effect of 1 for the prevention of cervical cancer in cell culture models. It was found that 1 inhibited cell viability by inducing apoptosis, as evidenced by the formation of apoptotic bodies, generation of reactive oxygen species (ROS), and the accumulation of cells in the sub-G1 phase. Treatment with compound 1 decreased the cell growth in a dose-dependent manner with an IC(50) value of 37.8 microM. Aesculetin-induced apoptosis was correlated with mitochondrial dysfunction (DeltaPsi(m)), leading to the release of cytochrome c from the mitochondria to the cytosol, as well as the proteolytic activation of caspases in HeLa cells. These results indicate that 1 induces apoptosis in HeLa cells through a ROS-mediated mitochondrial dysfunction pathway.
Yang
Jin
J
State Key Laboratory of Virology, College of Pharmacy, Wuhan University, Wuhan, China.
Xiao
Yu-Ling
YL
He
Xian-Ran
XR
Qiu
Guo-Fu
GF
Hu
Xian-Ming
XM
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D006690:Bisbenzimidazole; D020169:Caspases / Q000187:drug effects / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006367:HeLa Cells; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D008954:Models, Biological; D015394:Molecular Structure; D010946:Plants, Medicinal / Q000737:chemistry; D014407:Tumor Cells, Cultured; D014468:Umbelliferones / Q000737:chemistry / Q000494:pharmacology*; D002583:Uterine Cervical Neoplasms
D000972:Antineoplastic Agents, Phytogenic; D014468:Umbelliferones; D045304:Cytochromes c; D020169:Caspases; D006690:Bisbenzimidazole; C007628:esculetin