Nicotine inhibits cisplatin-induced apoptosis in NCI-H446 cells.
Nicotine is not only a major component in tobacco but is also a survival agonist that inhibits apoptosis induced by certain agents including chemotherapeutic drugs. Here, we first showed that nicotine inhibits cisplatin-induced apoptosis in NCI-H446 cells. An MTT assay, Annexin V-FITC staining, RT-PCR, and Western blot were applied to identify the viability of cells, stages of apoptosis, mRNA and signaling proteins expression, respectively. First, we observed that nicotine induced no significant apoptosis when used alone and promoted cell proliferation at a low concentration or for a short time, but the opposite was observed at a high concentration or for a long time. In addition, an increase in XIAP and Survivin mRNA or protein was observed. Next, when combined with cisplatin, growth inhibition rates were concentration dependent, decreased to the lowest level at first, but later climbed to the highest point. Furthermore, nicotine inhibited apoptosis induced by cisplatin and caused a concentration-dependent increase in both XIAP and Survivin mRNA or protein. Moreover, the apoptotic effect of the combination group was obviously higher than that of nicotine used alone at the same nicotine concentration and lower than that of cisplatin used alone at the same cisplatin concentration. These studies suggest that exposure to nicotine might negatively impact the apoptotic potential of chemotherapeutics.
Joint Laboratory of Immunogenomics, Zhoushan Hospital-Beijing Institute of Genomics Chinese Academy of Sciences, 238 Renming North Road, 316004 Dinghai, Zhejiang, China.
Fang
F
Zeng
Yun Cheng
YC
Li
Gang
G
Chen
Yong Kui
YK
Zhang
Ye Kai
YK
Wang
Shi Quan
SQ
Zhou
Li Na
LN
Ma
Ji Hang
JH
Zhou
Yan Yan
YY
Huang
Wang Yu
WY
Zhu
Xiao Guang
XG
Liu
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077022:Survivin; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000378:metabolism
D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D018722:Nicotinic Agonists; D000077022:Survivin; D051636:X-Linked Inhibitor of Apoptosis Protein; D009538:Nicotine; D002945:Cisplatin
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