Bee venom induced cell cycle arrest and apoptosis in human cervical epidermoid carcinoma Ca Ski cells.
Although it has been previously reported that bee venom (BV) can induce apoptosis in many cancer cell lines, there is no information on the effect of BV on human cervical cancer cells and its molecular mechanisms of action are not fully elucidated. In this study, the possible mechanisms of apoptosis by which BV acts on human cervical cancer Ca Ski cells were investigated. BV induced morphological changes and decreased the percentage of viable Ca Ski cells in a dose- and time-dependent manner. Flow cytometric analysis demonstrated that BV induced the production of reactive oxygen species, increased the level of cytoplasmic Ca2+, reduced mitochondrial membrane potential which led to cytochrome c release, and promoted the activation of caspase-3 which then led to apoptosis. BV also induced an increase in the levels of Fas, p53, p21 and Bax, but a decrease in the level of Bcl-2. The activities of both caspase-8 and caspase-9 were enhanced by BV, promoting caspase-3 activation, leading to DNA fragmentation. Based on the DNA fragmentation and DAPI staining, BV-induced apoptosis was mitochondrial-dependent and caspase-dependent. BV also promoted the expression of AIF and Endo G in the Ca Ski cells. Both AIF and Endo G proteins were released from the mitochondria, and then induced apoptosis which was not through activation of caspase. In conclusion, our data demonstrated that BV-induced apoptosis occurs via a Fas receptor pathway involving mitochondrial-dependent pathways and is closely related to the level of cytoplasmic Ca2+ in Ca Ski cells.
Ip
Siu-Wan
SW
Department of Nutrition, China Medical University, Taichung, Taiwan, ROC.
Wei
Hsiu-Chuan
HC
Lin
Jing-Pin
JP
Kuo
Hsiu-Maan
HM
Liu
Kuo-Ching
KC
Hsu
Shu-Chun
SC
Yang
Jai-Sing
JS
Mei-Dueyang
Chiu
Tsan-Hung
TH
Han
Sang-Mi
SM
Chung
Jing-Gung
JG
D017209:Apoptosis / Q000187:drug effects*; D001514:Bee Venoms / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects*; D017382:Reactive Oxygen Species; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000473:pathology
D001514:Bee Venoms; D017382:Reactive Oxygen Species; D002118:Calcium