Abstract
BackgroundWe 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).ResultsPentose 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.ConclusionsProteomic 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.
Highlights
We and others have previously reported that resveratrol (RSV) suppresses colon cancer cell proliferation and elevates apoptosis in vitro and/or in vivo, molecular mechanisms are not fully elucidated
We reported previously that RSV suppressed colon cancer cell proliferation and induced apoptosis even in the presence of Insulin-like Growth Factor-1 (IGF-1), a well-known growth factor elevated during obesity which has shown to enrich colon cancer stem cell populations [6,7]
We have previously shown that RSV suppressed IGF-1 signaling via suppression of IGF-1R resulting in G1 cell cycle arrest and suppression of proliferation in HT-29 and SW480 colon cancer cells [6]
Summary
We and others have previously reported that resveratrol (RSV) suppresses colon cancer cell proliferation and elevates apoptosis in vitro and/or in vivo, molecular mechanisms are not fully elucidated. RSV has been studied extensively as a chemopreventive/anti-proliferative agent in multiple cancer types including colon and prostate cancers [5,6]. We reported previously that RSV suppressed colon cancer cell proliferation and induced apoptosis even in the presence of IGF-1, a well-known growth factor elevated during obesity which has shown to enrich colon cancer stem cell populations [6,7]. RSV targets p53 and IGF-1R/Wnt signaling pathways to suppress colon cancer cell proliferation and induce apoptosis. The effects of RSV on metabolic pathways like the pentose phosphate pathway (PPP) and the cell-extracellular matrix (ECM) protein interaction, important in cancer cell growth and proliferation are not clearly understood
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