Nicotine inhibits apoptosis induced by cisplatin in human oral cancer cells.
Oral cancer demonstrates a strong epidemiological association with smoking, but little is known about the effect of nicotine on oral cancer cell apoptosis. Nicotine, a major component of cigarette smoke, can regulate cell proliferation and angiogenesis and suppress apoptosis induced by chemotherapeutic drugs. The main aim of this study was to investigate the effects of nicotine on apoptosis induced by cisplatin, which is commonly used to treat advanced oral cancers, in the human oral cancer cell line Tca8113. The cells were stimulated with nicotine in the presence or absence of cisplatin, and apoptosis was assayed. The results showed that nicotine inhibited apoptosis induced by cisplatin. It was also observed that survivin played a role in the inhibitory effect of nicotine on apoptosis. Depletion of survivin reduced the protective effect of nicotine against cisplatin-induced apoptosis. Akt, a physiological survivin kinase, is activated by nicotine. Treatment of Tca8113 cells with the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 blocked nicotine-induced survivin expression and enhanced cell apoptosis. These studies suggest that exposure to nicotine might negatively impact on the apoptotic potential of chemotherapeutic drugs, and that survivin plays a key role in the anti-apoptotic effect of nicotine. The Akt pathway may be required for nicotine function.
Xu
J
J
Department of Oral & Maxillofacial Surgery, The Second Affiliated Hospital, Sun Yat-Sen University, 107 Yanjiang West Road, Guangzhou 510120, China.
Huang
H
H
Pan
C
C
Zhang
B
B
Liu
X
X
Zhang
L
L
D000970:Antineoplastic Agents / Q000037:antagonists & inhibitors* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000037:antagonists & inhibitors* / Q000627:therapeutic use; D004347:Drug Interactions; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D009062:Mouth Neoplasms / Q000188:drug therapy / Q000378:metabolism; D009363:Neoplasm Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D051058:Oncogene Protein v-akt / Q000187:drug effects / Q000378:metabolism; D034741:RNA, Small Interfering / Q000187:drug effects / Q000378:metabolism; D000077022:Survivin
D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D018722:Nicotinic Agonists; D034741:RNA, Small Interfering; D000077022:Survivin; D009538:Nicotine; D051058:Oncogene Protein v-akt; D002945:Cisplatin