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

Sujin Kim; Wonki Kim; Do-Hee Kim; Jeong-Hoon Jang; Su-Jung Kim; Sin-Aye Park; Hyunggu Hahn; Byung Woo Han; Hye-Kyung Na; Kyung-Soo Chun; Bu Young Choi; Young-Joon Surh

doi:10.1016/j.abb.2020.108413

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

Arch Biochem Biophys. 2020 Aug 15:689:108413. doi: 10.1016/j.abb.2020.108413. Epub 2020 May 27.

Authors

Affiliations

¹ Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, South Korea; Tumor Microenvironment Global Core Research Center, College of Pharmacy, Seoul National University, Seoul 08826, South Korea.
² Tumor Microenvironment Global Core Research Center, College of Pharmacy, Seoul National University, Seoul 08826, South Korea.
³ Department of Chemistry, College of Convergence and Integrated Science, Kyonggi University, Suwon, Gyeonggi-do 16227, South Korea.
⁴ Department of Biomedical Laboratory Science, College of Medical Sciences, Soonchunhyang University, Asan 31538, South Korea.
⁵ Department of Food Science and Biotechnology, College of Knowledge-based Services Engineering, Sungshin Women's University, Seoul 01133, South Korea.
⁶ Department of Pharmacy, College of Pharmacy, Keimyung University, Daegu 42601, South Korea.
⁷ Department of Pharmaceutical Science and Engineering, Seowon University, Cheongju, Chungbuk 28674, South Korea. Electronic address: bychoi@seowon.ac.kr.
⁸ Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul 08826, South Korea; Tumor Microenvironment Global Core Research Center, College of Pharmacy, Seoul National University, Seoul 08826, South Korea; Cancer Research Institute, Seoul National University, Seoul 03080, South Korea. Electronic address: surh@snu.ac.kr.

PMID: 32473133
DOI: 10.1016/j.abb.2020.108413

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.

Keywords: Cancer chemoprevention; Gastric cancer; PIM-1; Resveratrol.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell Line, Tumor
Cell Proliferation / drug effects*
Cell Survival / drug effects
Humans
Protein Kinase Inhibitors / pharmacology*
Proto-Oncogene Proteins c-pim-1 / antagonists & inhibitors*
Proto-Oncogene Proteins c-pim-1 / metabolism
Resveratrol / pharmacology*
Stomach Neoplasms / drug therapy*
Stomach Neoplasms / metabolism

Substances

Protein Kinase Inhibitors
Proto-Oncogene Proteins c-pim-1
Resveratrol