title: Nicotine promotes cell proliferation and induces resistance to cisplatin by α7 nicotinic acetylcholine receptor‑mediated activation in Raw264.7 and El4 cells.
abstract: Although nicotine is a risk factor for carcinogenesis and atherosclerosis, epidemiological data indicate that nicotine has therapeutic beneﬁts in treating Alzheimer's disease. Our previous studies also showed that nicotine-treated dendritic cells have potential antitumor effects. Hence, the precise effects of nicotine on the biological characterizations of cells are controversial. The aim of the present study was to assess the roles of α7 nicotinic acetylcholine receptors (nAChRs), Erk1/2-p38-JNK and PI3K-Akt pathway in nicotine-mediated proliferation and anti-apoptosis effects. The results firstly showed that nicotine treatment clearly augmented cell viability and upregulated PCNA expression in both Raw264.7 and El4 cells. Meanwhile, nicotine afforded protection against cisplatin-induced toxicity through inhibiting caspase-3 activation and upregulating anti-apoptotic protein expression. Further exploration demonstrated that nicotine efficiently abolished cisplatin-promoted mitochondria translocation of Bax and the release of cytochrome c. The pretreatment of α-bungarotoxin and tubocurarine chloride significantly attenuated nicotine-augmented cell viability, abolished caspase-3 activation and α7 nAChR upregulation. Both Erk-JNK-p38 and PI3K-Akt signaling pathways could be activated by nicotine treatment in Raw264.7 and El4 cells. Notably, when Erk-JNK and PI3K-Akt activities were inhibited, nicotine-augmented cell proliferation and anti-apoptotic effects were abolished accordingly. The results presented here indicate that nicotine could achieve α7 nAChR-mediated proliferation and anti-apoptotic effects by activating Erk-JNK and PI3K-Akt pathways respectively, providing potential therapeutic molecules to deal with smoking-associated human diseases.
authors.affiliation: Basic Medicine Science, Medical College, Xiamen University, Xiamen, Fujian 361005, P.R. China.
authors.forename: Yan Yan
authors.initials: YY
authors.lastname: Wang
authors.affiliation: Basic Medicine Science, Medical College, Xiamen University, Xiamen, Fujian 361005, P.R. China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Basic Medicine Science, Medical College, Xiamen University, Xiamen, Fujian 361005, P.R. China.
authors.forename: Xiao Yan
authors.initials: XY
authors.lastname: Ni
authors.affiliation: Basic Medicine Science, Medical College, Xiamen University, Xiamen, Fujian 361005, P.R. China.
authors.forename: Zhen Huan
authors.initials: ZH
authors.lastname: Bai
authors.affiliation: Basic Medicine Science, Medical College, Xiamen University, Xiamen, Fujian 361005, P.R. China.
authors.forename: Qiong Yun
authors.initials: QY
authors.lastname: Chen
authors.affiliation: Basic Medicine Science, Medical College, Xiamen University, Xiamen, Fujian 361005, P.R. China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Basic Medicine Science, Medical College, Xiamen University, Xiamen, Fujian 361005, P.R. China.
authors.forename: Feng Guang
authors.initials: FG
authors.lastname: Gao
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002945:Cisplatin / Q000494:pharmacology*; D045304:Cytochromes c / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D006801:Humans; D020935:MAP Kinase Signaling System; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D021381:Protein Transport; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; C579095:MCL1 protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D018722:Nicotinic Agonists; D019253:Proto-Oncogene Proteins c-bcl-2; D064569:alpha7 Nicotinic Acetylcholine Receptor; D009538:Nicotine; D045304:Cytochromes c; D002945:Cisplatin