Apoptosis induction of human lung carcinoma cells by Chan Su (Venenum Bufonis) through activation of caspases.
Chan Su is a traditional Chinese medicine prepared from the dried white secretion of the auricular and skin glands of toads, and has been used as an oriental drug for the treatment of a number of diseases, including cancer. In this study, the potential of Chan Su (skin of Venenum Bufonis) to induce apoptosis in human lung carcinoma A549 cells was investigated. Treatment of A549 cells with skin of Venenum Bufonis resulted in the inhibition of cell growth and viability and the induction of apoptosis, which was shown by trypan blue counts, MTT assay, DAPI staining and flow cytometry analysis. The increase in apoptosis that was induced by skin of Venenum Bufonis was correlated with down-regulation of anti-apoptotic Bcl-2 expression, up-regulation of pro-apoptotic Fas ligand and death receptor 4, and a decrease in the mitochondrial membrane potential. Skin of Venenum Bufonis treatment induced the proteolytic activation of caspases and a concomitant degradation of poly(ADP-ribose)-polymerase and beta-catenin protein. Cleavage of Bid and a down-regulation of the inhibitor of apoptosis family proteins were also observed in skin of Venenum Bufonis-treated A549 cells. Data from this study indicates that SVB induces the apoptosis of A549 cells through a signaling cascade of death receptor-mediated extrinsic and mitochondria-mediated intrinsic caspase pathways.
Yun
Hye Ri
HR
Department of Biochemistry, College of Oriental Medicine, Dongeui University, Busan, Republic of Korea.
Yoo
Hwa Seung
HS
Shin
Dong Yeok
DY
Hong
Su Hyun
SH
Kim
Jong-Hwan
JH
Cho
Chong Kwan
CK
Choi
Yung Hyun
YH
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002018:Bufanolides / Q000494:pharmacology*; D002025:Bufonidae; D002277:Carcinoma / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology*; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology*; D015398:Signal Transduction / Q000187:drug effects
D002018:Bufanolides; C095591:chan su; D020169:Caspases