Alpha-tomatine induces apoptosis and inhibits nuclear factor-kappa B activation on human prostatic adenocarcinoma PC-3 cells

Lee, S.T.; Wong, P.F.; Cheah, S.C.; Mustafa, M.R. (2011) Alpha-tomatine induces apoptosis and inhibits nuclear factor-kappa B activation on human prostatic adenocarcinoma PC-3 cells. PLoS One, 6 (4). e18915. ISSN 1932-6203

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    Abstract

    Background: Alpha-tomatine (a-tomatine) is the major saponin in tomato (Lycopersicon esculentum). This study investigates the chemopreventive potential of a-tomatine on androgen-independent human prostatic adenocarcinoma PC-3 cells. Methodology/Principal Findings: Treatment of highly aggressive human prostate cancer PC-3 cells with a-tomatine resulted in a concentration-dependent inhibition of cell growth with a half-maximal efficient concentration (EC50) value of1.6760.3 mM. 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 a-tomatine exhibited its cytotoxic effects against PC-3 cells as early as an hour after treatment. The inhibitory effect of a-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 a 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-kB) nuclear translocation was inhibited, which in turn resulted in significant decreased in NF-kB/p50 and NF-kB/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 a-tomatine Conclusion/Significance: a-tomatine induces apoptosis and inhibits NF-kB activation on prostate cancer cells. These results suggest that a-tomatine may be beneficial for protection against prostate cancer development and progression.

    Item Type: Article
    Creators:
    1. Lee, S.T.
    2. Wong, P.F.
    3. Cheah, S.C.
    4. Mustafa, M.R.
    Journal or Publication Title: PLoS One
    Additional Information: Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
    Subjects: R Medicine > RM Therapeutics. Pharmacology
    Divisions: Faculty of Medicine
    Depositing User: Ms Haslinda Lahuddin
    Date Deposited: 17 Jan 2012 08:54
    Last Modified: 11 Dec 2013 15:12
    URI: http://eprints.um.edu.my/id/eprint/2440

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