Berberine induced apoptosis via promoting the expression of caspase-8, -9 and -3, apoptosis-inducing factor and endonuclease G in SCC-4 human tongue squamous carcinoma cancer cells.
Many phytochemicals have been recognized to have potential chemopreventive or chemotherapeutic efficacy in cancer treatment. In this study, we hypothesized that berberine would have anticancer activities in SCC-4 human tongue cancer cells. Results indicated that berberine reduced the viability of SCC-4 cells, which was initiated by the generation of reactive oxygen species, via an increase in cytosolic Ca(2+). Berberine-induced apoptosis was associated with a reduction of the mitochondrial membrane potential associated with changes in the Bax/Bcl-2 ratio, release of cytochrome c from mitochondria and activation of down stream caspase-3. Real-time PCR showed that berberine stimulated gene expression of caspase-8, -9 and -3, apoptosis-inducing factor and endonuclease G. The present study demonstrated that berberine-mediated apoptosis of SCC-4 cells is regulated by ROS, mitochondria, caspase-3-dependent and mitochondria-dependent pathways, suggesting that berberine may be considered for future studies as a promising therapeutic candidate for human tongue cancer.
Graduate Institute of Chinese Medical Science, China Medical University, Taichung 404, Taiwan.
Yung-Tsuan
YT
Ho
Chi-Cheng
CC
Lu
Jai-Sing
JS
Yang
Jo-Hua
JH
Chiang
Tsai-Chung
TC
Li
Siu-Wan
SW
Ip
Te-Chun
TC
Hsia
Ching-Lung
CL
Liao
Jaung-Geng
JG
Lin
W Gibson
WG
Wood
Jing-Gung
JG
Chung
D017209:Apoptosis / Q000187:drug effects*; D051033:Apoptosis Inducing Factor / Q000096:biosynthesis* / Q000235:genetics; D001599:Berberine / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020169:Caspases / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D003600:Cytosol / Q000378:metabolism; D004249:DNA Damage; D004706:Endodeoxyribonucleases / Q000096:biosynthesis* / Q000235:genetics; D005434:Flow Cytometry; D006801:Humans; D007527:Isoenzymes; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D014062:Tongue Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
C494829:AIFM1 protein, human; D051033:Apoptosis Inducing Factor; D007527:Isoenzymes; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D001599:Berberine; D004706:Endodeoxyribonucleases; C052391:endonuclease G; D020169:Caspases; D002118:Calcium