Caffeic acid induces apoptosis in human cervical cancer cells through the mitochondrial pathway
Wei-Chun Chang1, Ching-Hung Hsieh, Meen-Woon Hsiao
1Department of Obstetrics and Gynecology, School of Medicine China Medical University Hospital, Taichung, Taipei, Taiwan.
Objective:
The anti-proliferation effect of caffeic acid (3,4-dihydroxycinnamic acid), isolated from Ocimum gratissimum Linn, on human cervical cancer cells (HeLa cells) was examined to elucidate the associated mechanism and death mode.
Materials And Methods:
Flow cytometry showed that caffeic acid treatment results in dramatically increased apoptosis of HeLa cells. Western blot analysis revealed that caffeic acid activates various processed caspases.
Results:
Caffeic acid significantly reduced proliferation of HeLa cells in a concentration-dependent manner. Morphological evidence of apoptosis, including nuclei fragmentation was clearly observed 24 and 48 hours after exposure to caffeic acid (1 mM and 10 mM) by flow cytometry. Time-dependent inhibition was also observed. Caffeic acid decreased levels of uncleaved caspase-3 and Bcl-2, and induced cleaved caspase-3 and p53.
Conclusion:
Caffeic acid induces apoptosis by inhibiting Bcl-2 activity, leading to release of cytochrome c and subsequent activation of caspase-3, indicating that caffeic acid induces apoptosis via the mitochondrial apoptotic pathway. This also suggests that caffeic acid has a strong anti-tumor effect and may be a promising chemopreventive or chemotherapeutic agent.
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