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Resveratrol suppresses human colon cancer cell proliferation and induces apoptosis via targeting the pentose phosphate and the talin-FAK signaling pathways-A proteomic approach

Jairam Vanamala12*, Sridhar Radhakrishnan1, Lavanya Reddivari1, Vadiraja B Bhat35 and Andrey Ptitsyn4

Author Affiliations

1 Department of Food Science and Human Nutrition, Colorado State University, Fort Collins, Colorado, USA

2 Cancer Prevention and Control Program, University of Colorado Cancer Center, Aurora, Colorado, USA

3 Department of Pathology, Scott & White Hospital, Temple, Texas, USA

4 Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, USA

5 Agilent Technologies, Wilmington, Delaware, USA

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Proteome Science 2011, 9:49  doi:10.1186/1477-5956-9-49

Published: 17 August 2011

Abstract

Background

We and others have previously reported that resveratrol (RSV) suppresses colon cancer cell proliferation and elevates apoptosis in vitro and/or in vivo, however molecular mechanisms are not fully elucidated. Particularly, little information is available on RSV's effects on metabolic pathways and the cell-extra cellular matrix (ECM) communication that are critical for cancer cell growth. To identify important targets of RSV, we analyzed whole protein fractions from HT-29 advanced human colon cancer cell line treated with solvent control, IGF-1 (10 nM) and RSV (150 μM) using LC/MS/MS-Mud PIT (Multidimensional Protein Identification Technology).

Results

Pentose phosphate pathway (PPP), a vital metabolic pathway for cell cycle progression, was elevated and suppressed by IGF-1 and RSV, respectively in the HT-29 cell line. Enzymatic assays confirmed RSV suppression of glucose-6 phosphate dehydrogenase (rate limiting) and transketolase, key enzymes of the PPP. RSV (150 μM) suppressed, whereas IGF-1 (10 nM) elevated focal adhesion complex (FAC) proteins, talin and pFAK, critical for the cell-ECM communication. Western blotting analyses confirmed the suppression or elevation of these proteins in HT-29 cancer cells treated with RSV or IGF-1, respectively.

Conclusions

Proteomic analysis enabled us to establish PPP and the talin-pFAK as targets of RSV which suppress cancer cell proliferation and induce apoptosis in the colon cancer cell line HT-29. RSV (150 μM) suppressed these pathways in the presence and absence of IGF-1, suggesting its role as a chemo-preventive agent even in obese condition.

Keywords:
Resveratrol; Proteomics; Talin; Focal Adhesion Kinase (FAK); Pentose Phosphate Pathway; Insulin-like Growth Factor-1 (IGF-1)