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...
Saved in:
Main Authors: | , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science
2011
|
Subjects: | |
Online Access: | http://eprints.um.edu.my/2440/1/journal.pone.0018915.pdf http://eprints.um.edu.my/2440/ |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
Summary: | 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. |
---|