Realgar-induced apoptosis of cervical cancer cell line Siha via cytochrome c release and caspase-3 and caspase-9 activation

• Published in: Chinese journal of integrative medicine Vol. 18; no. 5; pp. 359 - 365
• Main Authors: Cheng, Yan-xiang, Liu, Rong, Wang, Qin, Li, Bing-shu, Xu, Xue-xian, Hu, Min, Chen, Lu, Fu, Qiong, Pu, De-min, Hong, Li
• Format: Journal Article
• Language: English
• Published: Heidelberg Chinese Association of Traditional and Western Medicine 01.05.2012
• Subjects: Apoptosis - drug effects; Apoptosis - physiology; Arsenicals - pharmacology; Caspase 3 - metabolism; Caspase 8 - metabolism; Caspase 9 - metabolism; Caspase Inhibitors; Cell Line, Tumor; Cell Survival - drug effects; Cell Survival - physiology; Cytochromes c - metabolism; Dose-Response Relationship, Drug; Enzyme Activation - drug effects; Enzyme Inhibitors - pharmacology; Female; Fluorescence Resonance Energy Transfer; Humans; Medicine; Medicine & Public Health; Original Article; Sulfides - pharmacology; Uterine Cervical Neoplasms - drug therapy; Uterine Cervical Neoplasms - metabolism; Uterine Cervical Neoplasms - pathology; apoptosis; realgar; cytochrome c; cervical cancer; caspases
• ISSN: 1672-0415; 1993-0402
• DOI: 10.1007/s11655-011-0697-z

Objective To explore the molecular mechanism of realgar-induced apoptosis of cervical cancer cells. Methods The cervical cancer cell line Siha was used to determine the cell viability and apoptosis after treatment with realgar using MTT assay and flow cytometry. The activities of caspase-3, -8, and -9 were detected by fluorescence resonance energy transfer technology and colorimetric assay, while the levels of Bcl-2, cytochrome c, and Bax were detected by Western blot method. Results Induction of apoptosis by realgar was detected in Siha cell line in a dose-dependent manner. The apoptosis was accompanied by a significant increase in cytochrome c release and activation of caspase-3 and caspase-9 but not caspase-8. Further, the realgar-induced apoptosis was inhibited by a broad-spectrum caspase inhibitor, a caspase-3 inhibitor, and a caspase-9 inhibitor but not by a caspase-8 inhibitor. Bcl-2 and Bax protein expressions were not changed by realgar. Conclusion The induction of apoptosis by realgar is mediated through a cytochrome c-dependent pathway, which sequentially activates caspase-9 and caspase-3.