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Proanthocyanidin from grape seeds inactivates the PI3-kinase/PKB pathway and induces apoptosis in a colon cancer cell
A-M Engelbrecht1, M Mattheyse, B Ellis
1Department of Physiological Sciences, Stellenbosch University, Stellenbosch, South Africa. ame@sun.ac.za
Abstract:
The aim of this investigation was to evaluate the chemopreventative/antiproliferative potential of a grape seed proanthocyanidin extract (GSPE) against colon cancer cells (CaCo2 cells) and to investigate its mechanism of action. GSPE (10-100 microg/ml) significantly inhibited cell viability and increased apoptosis in CaCo2 cells, but did not alter viability in the normal colon cell line (NCM460). The increased apoptosis observed in GSPE-treated CaCo2 cells correlated with an attenuation of PI3-kinase (p110 and p85 subunits) and decreased PKB Ser(473) phosphorylation. GSPE might thus exert its beneficial effects by means of increased apoptosis and suppression of the important PI3-kinase survival-related pathway.
Insights
Grape seed proanthocyanidin extract (GSPE) shows chemopreventative potential against colon cancer. GSPE inhibited colon cancer cell viability and increased apoptosis by suppressing the PI3-kinase survival pathway.
Area of Science:
- Oncology
- Molecular Biology
- Natural Products Chemistry
Background:
- Colon cancer remains a significant global health challenge.
- Chemoprevention using natural compounds offers a promising strategy.
- Grape seed proanthocyanidin extract (GSPE) is rich in bioactive polyphenols.
Purpose of the Study:
- To evaluate the chemopreventative and antiproliferative effects of GSPE on colon cancer cells (CaCo2).
- To elucidate the mechanism of action of GSPE in colon cancer cells.
Main Methods:
- Treatment of CaCo2 cells and normal colon cells (NCM460) with varying concentrations of GSPE.
- Assessment of cell viability using standard assays.
- Induction of apoptosis and analysis of key proteins in the PI3-kinase pathway (PI3K, PKB).
Main Results:
- GSPE significantly inhibited viability and induced apoptosis in CaCo2 cells.
- GSPE did not affect the viability of normal colon cells (NCM460).
- Apoptosis induction correlated with reduced PI3-kinase signaling (p110, p85 subunits) and decreased PKB phosphorylation.
Conclusions:
- GSPE exhibits selective antiproliferative effects against colon cancer cells.
- GSPE exerts its beneficial effects through enhanced apoptosis.
- GSPE suppresses the PI3-kinase/PKB survival pathway, suggesting a potential chemopreventative role.
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