Alpha-Tomatine Induces Apoptosis and Inhibits Nuclear Factor-Kappa B Activation on Human Prostatic Adenocarcinoma PC-3 Cells

Background: Alpha-tomatine (alpha-tomatine) is the major saponin in tomato (Lycopersicon esculentum). This study investigates the chemopreventive potential of alpha-tomatine on androgen-independent human prostatic adenocarcinoma PC-3 cells. Methodology/Principal Findings: Treatment of highly aggressive human prostate cancer PC-3 cells with alpha-tomatine resulted in a concentration-dependent inhibition of cell growth with a half-maximal efficient concentration (EC(50)) value of 1.67+/-0.3 mu M. It is also less cytotoxic to normal human liver WRL-68 cells and normal human prostate RWPE-1 cells. Assessment of real-time growth kinetics by cell impedance-based Real-Time Cell Analyzer (RTCA) showed that alpha-tomatine exhibited its cytotoxic effects against PC-3 cells as early as an hour after treatment. The inhibitory effect of alpha-tomatine on PC-3 cancer cell growth was mainly due to induction of apoptosis as evidenced by positive Annexin V staining and decreased in mitochondrial membrane potential but increased in nuclear condensation, polarization of F-actin, cell membrane permeability and cytochrome c expressions. Results also showed that alpha-tomatine induced activation of caspase-3, -8 and -9, suggesting that both intrinsic and extrinsic apoptosis pathways are involved. Furthermore, nuclear factor-kappa B (NF-kappa B) nuclear translocation was inhibited, which in turn resulted in significant decreased in NF-kappa B/p50 and NF-kappa B/p65 in the nuclear fraction of the treated cells compared to the control untreated cells. These results provide further insights into the molecular mechanism of the anti-proliferative actions of alpha-tomatine. Conclusion/Significance: alpha-tomatine induces apoptosis and inhibits NF-kappa B activation on prostate cancer cells. These results suggest that alpha-tomatine may be beneficial for protection against prostate cancer development and progression.