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Nicotine induces cell survival and chemoresistance by stimulating Mcl‐1 phosphorylation and its interaction with Bak in lung cancer
Author(s) -
Liu Ling,
Shi Xiaqing,
Zhao Huandong,
Yang Manyi,
Wang Chengzhi,
Liao Mingmei,
Zhao Jinfeng
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.28251
Subject(s) - nicotine , lung cancer , cancer research , phosphorylation , cancer , metastasis , cancer cell , medicine , cell growth , cell , drug resistance , pharmacology , drug , carcinogen , biology , microbiology and biotechnology , biochemistry
Nicotine is a major carcinogen in cigarettes, which can enhance cell proliferation and metastasis and increase the chemoresistance of cancer cells. Our previous data found that nicotine promotes cell survival in lung cancer by affecting the expression of antiapoptotic protein Mcl‐1, suggesting that the Mcl‐1 may be a therapeutic target for patients with lung cancer. In this study, we found that the effects of drug resistance on nicotine‐induced lung cancer cell lines were shown to influence the phosphorylation of Mcl‐1. Moreover, nicotine induces Mcl‐1 phosphorylation exclusively at the T163 site, which results in enhancement of the antiapoptotic activity of Mcl‐1 and increased cell survival. Meanwhile, nicotine can reduce the sensitivity of H1299 cells to CDDP via enhancement of the binding of Mcl‐1 to Bak, which inhibits the proapoptotic effect of Bak and ultimately leads to increased survival and drug resistance of lung cancer cells. Thus, nicotine‐induced cell survival and chemoresistance may occur in a mechanism by stimulating Mcl‐1 phosphorylation and its interaction with Bak, which may contribute to improving the efficacy of chemotherapy in the treatment of human lung cancer.