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Grape Seed Extract Potentiates Resveratrol Induced Human Cancer Cell Apoptosis via Activation of p53‐Dependent Signaling Pathway
Author(s) -
Radhakrishnan Sridhar,
Reddivari Lavanya,
Das Undurti N,
Sclafani Robert,
Vanamala Jairam
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.235.7
Subject(s) - apoptosis , reactive oxygen species , grape seed extract , downregulation and upregulation , programmed cell death , resveratrol , cancer research , cancer cell , chemistry , caspase , signal transduction , biology , cancer , microbiology and biotechnology , biochemistry , medicine , genetics , alternative medicine , pathology , gene
Grape seed extract (GSE) and resveratrol (RSV) combination synergistically suppressed proliferation and induced apoptosis in HCT‐116 colon cancer cells with upregulation of p53 and Bax: Bcl‐2 ratio. We hypothesized that GSE (≤ 50 μg/ml) might potentiate RSV (~25 μM) to upregulate apoptosis via elevation of reactive oxygen species (ROS) & p53 dependent mitochondrial apoptotic pathway. P53 inhibition by pithifrin‐α, a transcriptional inhibitor, attenuated RSV‐GSE induced apoptosis in HCT‐116 p53 +/+ comparable to p53 −/− cells. Reactive oxygen species (ROS) suppression by N‐acetyl cysteine attenuated apoptosis induced by the combination, indicating RSV‐GSE might activate p53 via ROS induction and subsequent DNA damage. Inhibition of caspases (3 & 8) confirmed that RSV‐GSE induced apoptosis involves caspase‐3 signaling (cell death detection ELISA). Selectivity towards cancer cells was confirmed by demonstrating that the RSV‐GSE is non‐toxic to a normal human CRL‐1831 colon cell line. RSV‐GSE suppressed proliferation and induced apoptosis even in the presence of mitogenic growth factor IGF‐1 (elevated during obesity), indicating its potential efficacy in obese conditions. In addition to its apoptotic properties, RSV‐GSE induced G 0 /G 1 phase arrest independent of p53 status. Thus, this study shows that the induction of apoptosis by RSV‐GSE in human colon cancer cells involves the ROS and p53 pathways. Grant Funding Source : This work was supported by College of Applied Human Sciences Challenge Grant, Colorado State University (2009–2010) and National Research Initiative Grant 2009‐55200‐05197 from the USDA National Institute for Food and Agriculture (2009–2012).