Berberine, a natural product, combined with cisplatin enhanced apoptosis through a mitochondria/caspase-mediated pathway in HeLa cells.
Berberine, a main component of Coptidis Rhizoma, has been extensively studied and is known to exhibit multiple pharmacologic activities. In this study, we investigated whether the combination of berberine and cisplatin exhibited significant cytotoxicity in HeLa cells. Apoptosis was evaluated based on DNA fragmentation and cytofluorometrically with the annexin-V/propidium iodide labeling method. Combined treatment with berberine and cisplatin acted in concert to induce loss of mitochondrial membrane potential (Delta Psi m), release of cytochrome-c from mitochondria, and decreased expression of antiapoptotic Bcl-2, Bcl-x/L, resulting in activation of caspases and apoptosis. Further study showed that cell death induced by the combined treatment was associated with increased reactive oxygen species generation and lipid peroxidation. Moreover, we discovered that the combined treatment-induced apoptosis was mediated by the activation of the caspase cascade. These results indicated that the potential of cytotoxicity mediated through the mitochondria-caspase pathway is primarily involved in the combined treatment-induced apoptosis.
Youn
Myung-Ja
MJ
VestibuloCochlear Research Center and Department of Microbiology, Wonkwang University, #344-2, Shinyoung-dong, Iksan, Jeonbuk 570-749, Korea.
So
Hong-Seob
HS
Cho
Hea-Joong
HJ
Kim
Hyung-Jin
HJ
Kim
Yunha
Y
Lee
Jeong-Han
JH
Sohn
Jung Sook
JS
Kim
Yong Kyu
YK
Chung
Sang-Young
SY
Park
Raekil
R
D000970:Antineoplastic Agents / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001599:Berberine / Q000494:pharmacology*; D020169:Caspases / Q000502:physiology*; D002945:Cisplatin / Q000494:pharmacology*; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D007202:Indicators and Reagents; D015227:Lipid Peroxidation / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013778:Tetrazolium Salts; D013844:Thiazoles
D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D007202:Indicators and Reagents; D017382:Reactive Oxygen Species; D013778:Tetrazolium Salts; D013844:Thiazoles; D001599:Berberine; D045304:Cytochromes c; D020169:Caspases; C022616:thiazolyl blue; D002945:Cisplatin