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...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science
2011
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| Online Access: | http://eprints.um.edu.my/2440/1/journal.pone.0018915.pdf |
| _version_ | 1796944863203164160 |
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| 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. |
| collection | UM |
| description | 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. |
| first_indexed | 2024-03-06T05:08:04Z |
| format | Article |
| id | um.eprints-2440 |
| institution | Universiti Malaya |
| language | English |
| last_indexed | 2024-03-06T05:08:04Z |
| publishDate | 2011 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | 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, |
| spellingShingle | 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 |
| title | 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_short | 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 |
| topic | RM Therapeutics. Pharmacology |
| url | http://eprints.um.edu.my/2440/1/journal.pone.0018915.pdf |
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