The Polycyclic Flavonoid, Maackiain, Arrests Cell Cycle Progression in LNCaP and PC‐3 Human Prostate Cancer Cells and Repairs DNA Damage in PC‐3 and NHPrE Cells

Abstract

The effect of maackiain, a potent polycyclic flavonoid with anticarcinogenic activities found in red clover, on cell proliferation, cell cycle progression and tumor suppressor gene expression was examined in human derived prostate cancer LNCaP and PC‐3 cells as well as normal human prostate epithelial (NHPrE) cells. The treatment of as low as 10 μM maackiain in LNCaP and PC‐3 cells for 3 days resulted in 20% inhibition of cell proliferation. The highest dosage of 100 uM resulted in 40% of growth inhibition in PC‐3 cells but 70% in LNCaP cells after 6 days treatment. Most importantly, for NHPrE cells, maackiain just began to be effective only at the highest concentration of 100 μM. The growth inhibition in maackiain treated LNCaP and PC‐3 cells was associated with cell cycle arrest at the G0/G1 and G2/M phases, respectively, in a dosage dependent manner without induction of apoptosis or senescence. The cell cycle arrest in maackiain treated PC‐3 cells was found to be resulted from enhanced expression of p21, p27 and hypophos‐Rb and suppressed expression of cyclin B and phos‐Rb. Immunofluorescence study using γH2A.X (phosphor S139) and DNA PKcs (phosphor T2647) antibodies indicated that maackiain treatments enhanced DNA damage repair both in PC‐3 and NHPrE cells without the activation of ATM or ATR signaling pathway. Our data suggest that maackiain may serve as a potential chemopreventitive agent against prostate cancer.