Alpha-tomatine induces apoptosis and inhibits nuclear factor-kappa B activation on human prostatic adenocarcinoma PC-3 cells
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...
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my.um.eprints.24402019-12-18T06:35:15Z http://eprints.um.edu.my/2440/ 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, Mohd Rais RM Therapeutics. Pharmacology 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. Public Library of Science 2011-04-26 Article PeerReviewed application/pdf en http://eprints.um.edu.my/2440/1/journal.pone.0018915.pdf Lee, S.T. and Wong, P.F. and Cheah, S.C. and Mustafa, Mohd Rais (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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RM Therapeutics. Pharmacology Lee, S.T. Wong, P.F. Cheah, S.C. Mustafa, Mohd Rais Alpha-tomatine induces apoptosis and inhibits nuclear factor-kappa B activation on human prostatic adenocarcinoma PC-3 cells |
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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. |
format |
Article |
author |
Lee, S.T. Wong, P.F. Cheah, S.C. Mustafa, Mohd Rais |
author_facet |
Lee, S.T. Wong, P.F. Cheah, S.C. Mustafa, Mohd Rais |
author_sort |
Lee, S.T. |
title |
Alpha-tomatine induces apoptosis and inhibits nuclear factor-kappa B activation on human prostatic adenocarcinoma PC-3 cells |
title_short |
Alpha-tomatine induces apoptosis and inhibits nuclear factor-kappa B activation on human prostatic adenocarcinoma PC-3 cells |
title_full |
Alpha-tomatine induces apoptosis and inhibits nuclear factor-kappa B activation on human prostatic adenocarcinoma PC-3 cells |
title_fullStr |
Alpha-tomatine induces apoptosis and inhibits nuclear factor-kappa B activation on human prostatic adenocarcinoma PC-3 cells |
title_full_unstemmed |
Alpha-tomatine induces apoptosis and inhibits nuclear factor-kappa B activation on human prostatic adenocarcinoma PC-3 cells |
title_sort |
alpha-tomatine induces apoptosis and inhibits nuclear factor-kappa b activation on human prostatic adenocarcinoma pc-3 cells |
publisher |
Public Library of Science |
publishDate |
2011 |
url |
http://eprints.um.edu.my/2440/1/journal.pone.0018915.pdf http://eprints.um.edu.my/2440/ |
_version_ |
1654960584467152896 |
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13.18916 |