Alpha-tomatine induces apoptosis and inhibits nuclear factor-kappa B activation on human prostatic adenocarcinoma
Sui-Ting Lee1, Pooi-Fong Wong, Shiau-Chuen Cheah
1Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
Background:
Alpha-tomatine (α-tomatine) is the major saponin in tomato (Lycopersicon esculentum). This study investigates the chemopreventive potential of α-tomatine on androgen-independent human prostatic adenocarcinoma PC-3 cells.
Methodology/Principal Findings:
Treatment of highly aggressive human prostate cancer PC-3 cells with α-tomatine resulted in a concentration-dependent inhibition of cell growth with a half-maximal efficient concentration (EC(50)) value of 1.67±0.3 µM. 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 α-tomatine exhibited its cytotoxic effects against PC-3 cells as early as an hour after treatment. The inhibitory effect of α-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 α-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-κB) nuclear translocation was inhibited, which in turn resulted in significant decreased in NF-κB/p50 and NF-κB/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 α-tomatine.
Conclusion/Significance:
α-tomatine induces apoptosis and inhibits NF-κB activation on prostate cancer cells. These results suggest that α-tomatine may be beneficial for protection against prostate cancer development and progression.
Insights
Alpha-tomatine, a compound from tomatoes, effectively inhibits prostate cancer cell growth by triggering apoptosis and blocking NF-κB signaling. This suggests potential chemopreventive benefits against prostate cancer.
Area of Science:
- Phytochemistry
- Cancer Biology
- Molecular Pharmacology
Background:
- Alpha-tomatine (α-tomatine) is a major saponin found in tomatoes (Lycopersicon esculentum).
- This study explores the potential of α-tomatine as a chemopreventive agent against prostate cancer.
- Focus is on androgen-independent human prostatic adenocarcinoma PC-3 cells.
Purpose of the Study:
- To investigate the chemopreventive potential of α-tomatine on human prostate cancer cells.
- To elucidate the molecular mechanisms underlying α-tomatine's anti-proliferative effects.
- To assess the compound's selective toxicity towards cancer cells versus normal cells.
Main Methods:
- Cell viability assays on PC-3, WRL-68, and RWPE-1 cell lines.
- Real-Time Cell Analyzer (RTCA) for growth kinetics.
- Apoptosis markers assessed: Annexin V staining, mitochondrial membrane potential, nuclear condensation, F-actin polarization, cytochrome c, and caspase activation (caspase-3, -8, -9).
- Nuclear factor-kappa B (NF-κB) translocation and expression analyzed.
Main Results:
- α-tomatine demonstrated concentration-dependent inhibition of PC-3 cell growth (EC50 = 1.67±0.3 µM).
- The compound showed lower cytotoxicity to normal liver (WRL-68) and prostate (RWPE-1) cells.
- α-tomatine induced apoptosis via both intrinsic and extrinsic pathways and inhibited NF-κB nuclear translocation and expression.
Conclusions:
- α-tomatine effectively induces apoptosis and inhibits NF-κB activation in prostate cancer cells.
- These findings suggest α-tomatine holds promise for prostate cancer prevention and treatment.
- Further research into α-tomatine's chemopreventive capabilities is warranted.
