Unlocking the Phytotherapeutic Synergism between Beta-lapachone and Soybean-derived Genistein in Human Prostate cancer cells

Prostate cancer after many years is still the second most common cancer in American
men with about 233,000 new cases and 29,480 deaths estimated to be occurring in 2014.
Despite the wide spectra of reports demonstrating the anti-cancer phytotherapeutic potentials of
beta-lapachone and soybean-derived genistein in various tumors, little emphasis had been placed
on their synergistic effects in androgen-independent PC3 and androgen-dependent LNCaP
prostate cancer cell lines. In this study, we aim to characterize the combined effects of genistein
and b-lapachone on the phyto/chemosensitivity of LNCaP and PC3 human prostate cancer cells
in-vitro, using MTT assay and LDH assay to study treatment-induced growth inhibition and
cytotoxicity. Annexin-V-FITC and PI-TUNEL assays were also used to determine the potential
treatment-induced apoptosis and/or necrosis.
Our results revealed that both PC3 and LNCaP are phytosensitive to both single and combined
treatments, though time-and dose-dependent. We observed that our treatments induced dual
death pathways-apoptosis and necrosis-in both cell types and also observed that growth
inhibition in both correlated positively with cell death in which, b-lapachone and genistein
induced cell cycle arrest at the G1 and/or S phase and G2–M checkpoints respectively.
Invariably, our results indicate that combination treatments with b-lapachone and genistein are
more potent in killing both PC3 and LNCaP cancer cells than treatment with either genistein or
b-lapachone alone. Our current results are therefore in agreement with the hypothesis that drugcombinations
that target cell cycles at different critical checkpoints are more effective in causing
cell death.