Nicotine prevents the apoptosis induced by menadione in human lung cancer cells.
Approximately 50% of long-term cigarette smokers die prematurely from the adverse effects of smoking, including on lung cancer and other illnesses. Nicotine is a main component in tobacco and has been implicated as a potential factor in the pathogenesis of human lung cancer. However, the mechanism of nicotine action in the development of lung cancer remains largely unknown. In the present study, we designed a nicotine-apoptosis system, by pre-treatment of nicotine making lung cancer cell A549 to be in a physiological nicotine environment, and observed that nicotine promoted cell proliferation and prevented the menadione-induced apoptosis, and exerts its role of anti-apoptosis by shift of apoptotic stage induced by menadione from late apoptotic stage to early apoptotic stage, in which NF-kappaB was up-regulated. Interference analysis of NF-kappaB in A549 cells showed that knock down of NF-kappaB resulted in apoptosis promotion and counteracted the protective effect of nicotine. The findings suggest that nicotine has potential effect in lung cancer genesis, especially in patients with undetectable early tumor development and development of specific NF-kappaB inhibitors would represent a potentially exciting new pharmacotherapy for tobacco-related lung cancer.
Zhang
Tao
T
Department of Genetics and Center for Developmental Biology, College of Life Sciences, Wuhan University, Wuhan 430072, PR China.
Lu
Heng
H
Shang
Xuan
X
Tian
Yihao
Y
Zheng
Congyi
C
Wang
Shiwen
S
Cheng
Hanhua
H
Zhou
Rongjia
R
D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D016328:NF-kappa B / Q000235:genetics; D009538:Nicotine / Q000494:pharmacology*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D024483:Vitamin K 3 / Q000494:pharmacology*
D016328:NF-kappa B; D012333:RNA, Messenger; D009538:Nicotine; D024483:Vitamin K 3