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Resveratrol suppresses gastric cancer cell proliferation and survival through inhibition of PIM-1 kinase activity

Cited 3 time in Web of Science Cited 2 time in Scopus
Authors
Kim, Sujin; Kim, Wonki; Kim, Do-Hee; Jang, Jeong-Hoon; Kim, Su-Jung; Park, Sin-Aye; Hahn, Hyunggu; Han, Byung Woo; Na, Hye-Kyung; Chun, Kyung-Soo; Choi, Bu Young; Surh, Young-Joon
Issue Date
2020-08
Citation
Archives of Biochemistry and Biophysics, Vol.689, p. 108413
Keywords
ResveratrolPIM-1Cancer chemopreventionGastric cancer
Abstract
The proviral integration site for Moloney murine leukemia virus (PIM) family of serine/threonine-specific kinases consist of three isoforms, that regulate proliferation, apoptosis, metabolism, invasion, and metastasis of cancer cells. Among these, abnormally elevated kinase activity of PIM-1 contributes to the progression of gastric cancer and predicts poor prognosis and a low survival rate in gastric cancer patients. In the present study, we found that resveratrol, one of the representative chemopreventive and anticarcinogenic phytochemicals, directly binds to PIM-1 and thereby inhibits its catalytic activity in human gastric cancer SNU-601 cells. This resulted in suppression of phosphorylation of the proapoptotic Bad, a known substrate of PIM-1. Resveratrol, by inactivating PIM-1, also inhibited anchorage-independent growth and proliferation of SNU-601 cells. To understand the molecular interaction between resveratrol and PIM-1, we conducted docking simulation and found that resveratrol directly binds to the PIM-1 at the ATP-binding pocket. In conclusion, the proapototic and anti-proliferative effects of resveratrol in gastric cancer cells are likely to be mediated through suppression of PIM-1 kinase activity, which may represent a novel mechanism underlying its chemopreventive and anticarcinogenic actions.
ISSN
0003-9861
URI
https://hdl.handle.net/10371/172568
DOI
https://doi.org/10.1016/j.abb.2020.108413
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Graduate School of Convergence Science and Technology (융합과학기술대학원)Dept. of Molecular and Biopharmaceutical Sciences (분자의학 및 바이오제약학과)Journal Papers (저널논문_분자의학 및 바이오제약학과)
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