We previously demonstrated that evening primrose extract (EPE) induced apoptosis in
Ehrlich ascites tumor cells (EATC), and this effect was specific on
tumor cells. Furthermore, our results demonstrated that EPE exposure elicited a rapid increase in the activity of
superoxide dismutase and intracellular
peroxides levels. These changes caused translocation of Bax to mitochondria and a subsequent release of mitochondrial
cytochrome c. However, no activation of
caspase-3 was observed in EPE-treated EATC. On the other hand,
apoptosis-inducing factor (AIF) was translocated from mitochondria to nuclei. The EPE-induced translocation of AIF was suppressed with the addition of
catalase, suggesting that the rapid intracellular
peroxide levels after addition of EPE triggers off induction of apoptosis, which is AIF-mediated and
caspase-independent. In this study, we have shown that EPE elicited a dose-dependent accumulation of cells in the G1 phase and inhibited
DNA synthesis. Our results also demonstrated that cell cycle arrest and inhibition of proliferation in EATC by EPE are associated with decreased Rb phosphorylation. Furthermore, inhibitions of Rb phosphorylation and
DNA synthesis by EPE were not suppressed with the addition of
catalase. The present study suggests that intracellular
peroxides, which trigger off induction of apoptosis, are not the trigger of EPE-induced G1 arrest in cell cycle.