Nicotine promotes cell proliferation and induces resistance to cisplatin by α7 nicotinic acetylcholine receptor‑mediated activation in Raw264.7 and El4 cells

Wang,Yan Yan; Liu,Yao; Ni,Xiao Yan; Bai,Zhen Huan; Chen,Qiong Yun; Zhang,Ye; Gao,Feng Guang

doi:10.3892/or.2013.2962

Nicotine promotes cell proliferation and induces resistance to cisplatin by α7 nicotinic acetylcholine receptor‑mediated activation in Raw264.7 and El4 cells

Authors:
- Yan Yan Wang
- Yao Liu
- Xiao Yan Ni
- Zhen Huan Bai
- Qiong Yun Chen
- Ye Zhang
- Feng Guang Gao
View Affiliations

Affiliations: Basic Medicine Science, Medical College, Xiamen University, Xiamen, Fujian 361005, P.R. China
Published online on: December 31, 2013 https://doi.org/10.3892/or.2013.2962
Pages: 1480-1488

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

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.

View Figures

View References

1	Printz C: Gap narrows in African American smoking-related cancers, increases in breast and colorectal cancers. Cancer. 117:23572011. View Article : Google Scholar : PubMed/NCBI
2	Li S, Peng Q, Chen Y, You J, Chen Z, Deng Y, Lao X, Wu H, Qin X and Zeng Z: DNA repair gene XRCC1 polymorphisms, smoking, and bladder cancer risk: a meta-analysis. PLoS One. 8:e734482013. View Article : Google Scholar : PubMed/NCBI
3	Albuquerque EX, Pereira EF, Alkondon M and Rogers SW: Mammalian nicotinic acetylcholine receptors: from structure to function. Physiol Rev. 89:73–120. 2009. View Article : Google Scholar : PubMed/NCBI
4	Cardinale A, Nastrucci C, Cesario A and Russo P: Nicotine: specific role in angiogenesis, proliferation and apoptosis. Crit Rev Toxicol. 42:68–89. 2012. View Article : Google Scholar : PubMed/NCBI
5	Tournier JM and Birembaut P: Nicotinic acetylcholine receptors and predisposition to lung cancer. Curr Opin Oncol. 23:83–87. 2011. View Article : Google Scholar : PubMed/NCBI
6	Guo L, Li L, Wang W, Pan Z, Zhou Q and Wu Z: Mitochondrial reactive oxygen species mediates nicotine-induced hypoxia-inducible factor-1α expression in human non-small cell lung cancer cells. Biochim Biophys Acta. 1822:852–861. 2012.PubMed/NCBI
7	Jin HJ, Li HT, Sui HX, Xue MQ, Wang YN, Wang JX and Gao FG: Nicotine stimulated bone marrow-derived dendritic cells could augment HBV specific CTL priming by activating PI3K-Akt pathway. Immunol Lett. 146:40–49. 2012. View Article : Google Scholar : PubMed/NCBI
8	Jin HJ, Sui HX, Wang YN and Gao FG: Nicotine up-regulated 4-1BBL expression by activating Mek-PI3K pathway augments the efficacy of bone marrow-derived dendritic cell vaccination. J lin Immunol. 33:246–254. 2013. View Article : Google Scholar : PubMed/NCBI
9	Gao FG, Wan DF and Gu JR: Ex vivo nicotine stimulation augments the efficacy of therapeutic bone marrow-derived dendritic cell vaccination. Clin Cancer Res. 13:3706–3712. 2007. View Article : Google Scholar
10	Changeux JP: The nicotinic acetylcholine receptor: the founding father of the pentameric ligand-gated ion channel superfamily. J Biol Chem. 287:40207–40215. 2012. View Article : Google Scholar : PubMed/NCBI
11	Matteoli G and Boeckxstaens GE: The vagal innervation of the gut and immune homeostasis. Gut. 62:1214–1222. 2013. View Article : Google Scholar : PubMed/NCBI
12	Al-Wadei MH, Al-Wadei HA and Schuller HM: Pancreatic cancer cells and normal pancreatic duct epithelial cells express an autocrine catecholamine loop that is activated by nicotinic acetylcholine receptors α3, α5, and α7. Mol Cancer Res. 10:239–249. 2012.PubMed/NCBI
13	Al-Wadei MH, Al-Wadei HA and Schuller HM: Effects of chronic nicotine on the autocrine regulation of pancreatic cancer cells and pancreatic duct epithelial cells by stimulatory and inhibitory neurotransmitters. Carcinogenesis. 33:1745–1753. 2012. View Article : Google Scholar : PubMed/NCBI
14	Wang S, Takayama K, Tanaka K, Takeshita M, Nakagaki N, Ijichi K, Li H and Nakanishi Y: Nicotine induces resistance to epidermal growth factor receptor tyrosine kinase inhibitor by α1 nicotinic acetylcholine receptor-mediated activation in PC9 cells. J Thorac Oncol. 8:719–725. 2013.
15	Lien YC, Wang W, Kuo LJ, Liu JJ, Wei PL, Ho YS, Ting WC, Wu CH and Chang YJ: Nicotine promotes cell migration through alpha7 nicotinic acetylcholine receptor in gastric cancer cells. Ann Surg Oncol. 18:2671–2679. 2011. View Article : Google Scholar : PubMed/NCBI
16	Wei PL, Kuo LJ, Huang MT, Ting WC, Ho YS, Wang W, An J and Chang YJ: Nicotine enhances colon cancer cell migration by induction of fibronectin. Ann Surg Oncol. 18:1782–1790. 2011. View Article : Google Scholar : PubMed/NCBI
17	Sun X, Ritzenthaler JD, Zhong X, Zheng Y, Roman J and Han S: Nicotine stimulates PPARβ/δ expression in human lung carcinoma cells through activation of PI3K/mTOR and suppression of AP-2α. Cancer Res. 69:6445–6453. 2009.
18	Paleari L, Sessa F, Catassi A, Servent D, Mourier G, Doria-Miglietta G, Ognio E, Cilli M, Dominioni L, Paolucci M, Calcaterra A, Cesario A, Margaritora S, Granone P and Russo P: Inhibition of non-neuronal α7-nicotinic receptor reduces tumorigenicity in A549 NSCLC xenografts. Int J Cancer. 125:199–211. 2009.
19	Paleari L, Negri E, Catassi A, Cilli M, Servent D, D’Angelillo R, Cesario A, Russo P and Fini M: Inhibition of nonneuronal α7-nicotinic receptor for lung cancer treatment. Am J Respir Crit Care Med. 179:1141–1150. 2009.
20	Shi D, Guo W, Chen W, Fu L, Wang J, Tian Y, Xiao X, Kang T, Huang W and Deng W: Nicotine promotes proliferation of human nasopharyngeal carcinoma cells by regulating α7AChR, ERK, HIF-1α and VEGF/PEDF signaling. PLoS One. 7:e438982012.PubMed/NCBI
21	Cesario A, Russo P, Nastrucci C and Granone P: Is α7-nAChR a possible target for lung cancer and malignant pleural mesothelioma treatment? Curr Drug Targets. 13:688–694. 2012.
22	Brown KC, Lau JK, Dom AM, Witte TR, Luo H, Crabtree CM, Shah YH, Shiflett BS, Marcelo AJ, Proper NA, Hardman WE, Egleton RD, Chen YC, Mangiarua EI and Dasgupta P: MG624, an α7-nAChR antagonist, inhibits angiogenesis via the Egr-1/FGF2 pathway. Angiogenesis. 15:99–114. 2012.
23	Hu SX, Sui HX, Jin HJ, Ni XY, Liu XX, Xue MQ, Zhang Y and Gao FG: Lipopolysaccharide and dose of nicotine determine the effects of nicotine on murine bone marrow-derived dendritic cells. Mol Med Rep. 5:1005–1010. 2012.PubMed/NCBI
24	Zhang SH and Huang Q: Etoposide induces apoptosis via the mitochondrial- and caspase-dependent pathways and in non-cancer stem cells in Panc-1 pancreatic cancer cells. Oncol Rep. 30:2765–2770. 2013.PubMed/NCBI
25	Park HY, Kim GY, Kwon TK, Hwang HJ, Kim ND, Yoo YH and Choi YH: Apoptosis induction of human leukemia U937 cells by 7,8-dihydroxyflavone hydrate through modulation of the Bcl-2 family of proteins and the MAPKs signaling pathway. Mutat Res. 751:101–108. 2013. View Article : Google Scholar : PubMed/NCBI
26	Zhu X, Jiang Y, Shan PF, Shen J, Liang QH, Cui RR, Liu Y, Liu GY, Wu SS, Lu Q, Xie H, Liu YS, Yuan LQ and Liao EY: Vaspin attenuates the apoptosis of human osteoblasts through ERK signaling pathway. Amino Acids. 44:961–968. 2013. View Article : Google Scholar : PubMed/NCBI
27	Chi J, Zhu Y, Fu Y, Liu Y, Zhang X, Han L, Yin X and Zhao D: Cyclosporin A induces apoptosis in H9c2 cardiomyoblast cells through calcium-sensing receptor-mediated activation of the ERK MAPK and p38 MAPK pathways. Mol Cell Biochem. 367:227–236. 2012. View Article : Google Scholar : PubMed/NCBI
28	Cucina A, Dinicola S, Coluccia P, Proietti S, D’Anselmi F, Pasqualato A and Bizzarri M: Nicotine stimulates proliferation and inhibits apoptosis in colon cancer cell lines through activation of survival pathways. J Surg Res. 178:233–241. 2012. View Article : Google Scholar : PubMed/NCBI
29	Kale J, Liu Q, Leber B and Andrews DW: Shedding light on apoptosis at subcellular membranes. Cell. 151:1179–1184. 2012. View Article : Google Scholar : PubMed/NCBI
30	Ferrer PE, Frederick P, Gulbis JM, Dewson G and Kluck RM: Translocation of a Bak C-terminus mutant from cytosol to mitochondria to mediate cytochrome C release: implications for Bak and Bax apoptotic function. PLoS One. 7:e315102012. View Article : Google Scholar : PubMed/NCBI
31	Bergstrom CL, Beales PA, Lv Y, Vanderlick TK and Groves JT: Cytochrome c causes pore formation in cardiolipin-containing membranes. Proc Natl Acad Sci USA. 110:6269–6274. 2013. View Article : Google Scholar : PubMed/NCBI
32	Li Y, Chen G, Zhao J, Nie X, Wan C, Liu J, Duan Z and Xu G: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) induces microglial nitric oxide production and subsequent rat primary cortical neuron apoptosis through p38/JNK MAPK pathway. Toxicology. 312:132–141. 2013. View Article : Google Scholar : PubMed/NCBI
33	Davis RJ: Signal transduction by the JNK group of MAP kinases. Cell. 103:239–252. 2000. View Article : Google Scholar : PubMed/NCBI
34	Faris M, Kokot N, Latinis K, Kasibhatla S, Green DR, Koretzky GA and Nel A: The c-Jun N-terminal kinase cascade plays a role in stress-induced apoptosis in Jurkat cells by up-regulating Fas ligand expression. J Immunol. 160:134–144. 1998.PubMed/NCBI
35	Minamino T, Christou H, Hsieh CM, Liu Y, Dhawan V, Abraham NG, Perrella MA, Mitsialis SA and Kourembanas S: Targeted expression of heme oxygenase-1 prevents the pulmonary inflammatory and vascular responses to hypoxia. Proc Natl Acad Sci USA. 98:8798–8803. 2001. View Article : Google Scholar : PubMed/NCBI