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Volume 2014, Article ID 215426, 7 pages
Review Article

Bcl2 Family Functions as Signaling Target in Nicotine-/NNK-Induced Survival of Human Lung Cancer Cells

Division of Cancer Biology, Department of Radiation Oncology, Emory University School of Medicine and Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA

Received 3 March 2014; Accepted 7 May 2014; Published 20 May 2014

Academic Editor: Patrick Auberger

Copyright © 2014 Xingming Deng. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Lung cancer is the leading cause of cancer death and has a strong etiological association with cigarette smoking. Nicotine and nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) are two major components in cigarette smoke that significantly contribute to the development of human lung cancer. Nicotine is able to stimulate survival of both normal human lung epithelial and lung cancer cells. In contrast to nicotine, NNK is a more potent carcinogen that not only induces single-strand DNA breaks and oxidative DNA damage but also stimulates survival and proliferation of normal lung epithelial and lung cancer cells. However, the molecular mechanism(s) by which nicotine and NNK promote cell survival, proliferation, and lung tumor development remains elusive. The fate of cells (i.e., survival or death) is largely decided by the Bcl2 family members. In the past several years, multiple signaling links between nicotine/NNK and Bcl2 family members have been identified that regulate survival and proliferation. This review provides a concise, systematic overview of the current understanding of the role of the pro- or antiapoptotic proteins in cigarette smoking, lung cancer development, and treatment resistance.