Vitexicarpin, a flavonoid from Vitex trifolia L., induces apoptosis in K562 cells via mitochondria-controlled apoptotic pathway

Objective: To investigate the inhibitory effect of vitexicarpin on the proliferation of human cancer cells and its mechanism of action.

Methods: The inhibitory effect of vitexicarpin on the proliferation of human cancer cells was evaluated by the SRB method and its apoptosis-inducing effect was demonstrated by morphological observation under light microscope, flow cytometric analysis and agarose gel electrophoresis. The proteins related to apoptosis were examined by Western blotting analysis.

Results: Vitexicarpin significantly inhibited the proliferation of human cancer cells, A2780, HCT-15, HT-1080 and K562, with the IC50 values of (19.1 +/- 2.4) micromol x L(-1) for A2780(48 h), (0.66 +/- 0.10) micromol x L(-1) for HCT-15(48 h), (0.44 +/- 0.06) micromol x L(-1) for HT-1080 (48 h) and (0.28 +/- 0.14) micromol x L(-1) for K562 (24 h). The cells treated with vitexicarpin showed characteristic morphology typical for apoptosis and gave dose-dependent sub-G0/G1 peak in the flow cytometric analysis and DNA ladder on agarose gel electrophoresis. In Western blotting analysis, the cleavage of PARP and caspase-3, the release of cytochrome c from mitochondria into the cytosol, the decrease of Bcl-2 expression level, and the down-regulation of the ratio of Bcl-2/Bax expression level were examined in the K562 cells treated with vitexicarpin.

Conclusions: Vitexicarpin induces apoptosis in K562 cells via mitochondria-controlled apoptotic pathway.