Coumarin induces cell cycle arrest and apoptosis in human cervical cancer HeLa cells through a mitochondria- and caspase-3 dependent mechanism and NF-kappaB down-regulation.
The effects of coumarin on cell viability, cell cycle arrest and induction of apoptosis were investigated in human cervical cancer HeLa cells. Coumarin was cytotoxic with an IC50 of 54.2 microM, induced morphological changes, and caused G0/G1 arrest and apoptosis. The decreasing number of viable cells appeared to be due to induction of cell cycle arrest and apoptotic cell death, since coumarin induced morphologically apoptotic changes and internucleosomal DNA laddering fragmentation and increased the sub-G1 group. Coumarin affected the production of reactive oxygen species and Ca2+ concentration, and dose-dependently induced the depolarization of mitochondrial membrane potential. Also, coumarin treatment gradually decreased the expression of G0/G1-associated proteins which may have led to the G0/G1 arrest, and the anti-apoptotic proteins Bcl-2 and Bcl-xL, and increased the expression of the pro-apoptotic protein Bax. Coumarin decreased the mitochondrial membrane potential and promoted the release of cytochrome c and the activation of caspase-3 before leading to apoptosis. These results provide information on the mechanisms by which coumarin induces cell cycle arrest and apoptosis in human cervical cancer cells (HeLa).
Chuang
Jing-Yuan
JY
Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, Taiwan, ROC.
Huang
Yung-Feng
YF
Lu
Hsu-Feng
HF
Ho
Heng-Chen
HC
Yang
Jai-Sing
JS
Li
Te-Mao
TM
Chang
Nai-Wen
NW
Chung
Jing-Gung
JG
D002118:Calcium / Q000378:metabolism; D053143:Caspase 2 / Q000378:metabolism*; D003374:Coumarins / Q000494:pharmacology*; D015536:Down-Regulation; D005260:Female; D006367:HeLa Cells; D006801:Humans; D008564:Membrane Potentials; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology*
D003374:Coumarins; D016328:NF-kappa B; D017382:Reactive Oxygen Species; C030123:coumarin; D053143:Caspase 2; D002118:Calcium