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Resveratrol regulates cellular PKC α and δ to inhibit growth and induce apoptosis in gastric cancer cells

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Summary

Resveratrol, a dietary phytoalexin, has emerged as a promising chemopreventive agent due to its antiproliferative and pro-apoptotic action toward cancer cells and its ability to inhibit tumor growth in animals. Gastric adenocarcinoma cells respond to resveratrol treatment with suppression of DNA synthesis, activation of nitric oxide synthase, induction of apoptosis and inhibition of total PKC and PKC α activity. Here we demonstrate that treatment of gastric adenocarcinoma SNU-1 cells with resveratrol results in time and concentration dependent accumulation of tumor suppressors p21(cip1/WAF -1) and p53 and is preceded by loss of membrane-associated PKC δ protein and a concomitant increase in cytosolic PKC α. Arrest of the cell cycle at transition of S to G2/M phases correlates with the profile of 3H-thymidine incorporation and accumulation of p21(cip1/WAF -1) and was temporally dependent on increase of p53. SNU-1 cells respond to resveratrol treatment with up-regulation of both Fas and Fas-L proteins, whereas in KATO-III cells, with deleted p53, only Fas-L is increased after resveratrol treatment. Although Fas and Fas-L proteins in SNU-1 cells and Fas-L in KATO-III cells were elevated within 24 h of cell treatment with low concentrations of resveratrol, significant apoptotic response at these concentrations was observed only after 48 h. Altogether, our findings indicate that resveratrol engages PKC α and δ signals in gastric adenocarcinoma SNU-1 cells prior to up-regulation of antiproliferative and pro-apoptotic signals. The specific cell death signals engaged by resveratrol appear to be cell type dependent and suggest that resveratrol has chemopreventive potential even after mutational changes have occurred.

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Authors and Affiliations

  1. Department of Medicine Division of Gastroenterology, Cook County Hospital, Chicago, IL, 60612, USA

    Mary Jo Atten, Ernesto Godoy-Romero, Bashar M. Attar, Matthew Zopel & Oksana Holian

  2. Department of Pathology, Cook County Hospital, Chicago, IL, 60612, USA

    Thomas Milson

  3. Division of Gastroenterology, Cook County Hospital, 1901 W. Harrison Street, Chicago, IL, 60612, USA

    Oksana Holian

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  1. Mary Jo Atten
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  2. Ernesto Godoy-Romero
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Correspondence to Oksana Holian.

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Atten, M.J., Godoy-Romero, E., Attar, B.M. et al. Resveratrol regulates cellular PKC α and δ to inhibit growth and induce apoptosis in gastric cancer cells. Invest New Drugs 23, 111–119 (2005). https://doi.org/10.1007/s10637-005-5855-8

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