期刊
FOOD AND CHEMICAL TOXICOLOGY
卷 81, 期 -, 页码 1-8出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.fct.2015.04.002
关键词
Capsaicin; DMBA/TPA; Skin inflammation; Tumorigenesis; COX-2; iNOS
资金
- National Natural Science Foundation of China [81173174, 81202655, 81403260]
- National Key Technology RD Program [2008BAI51B02]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
- Ph.D. Programs Foundation of Ministry of Education of the People's Republic of China [20113237110008]
- China Postdoctoral Science Foundation [2014M551639]
- Postdoctoral Science Foundation of Jiangsu province [1401138C]
- Jiangsu College Graduate Research and Innovation Projects [CXIX12_0587, KYZZ_0270]
Epidemiologic and animal studies revealed that capsaicin (8-methyl-N-vanillyl-6-noneamide) can act as a carcinogen or cocarcinogen. However, the influence of consumption of capsaicin-containing foods or vegetables on skin cancer patients remains largely unknown. In the present study, we demonstrated that capsaicin has a cocarcinogenic effect on 9, 10-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin tumorigenesis. Our results showed that topical application of capsaicin on the dorsal skin of DMBA-initiated and TPA-promoted mice could significantly accelerate tumor formation and growth and induce more and larger skin tumors than the model group (DMBA + TPA). Moreover, capsaicin could promote TPA-induced skin hyperplasia and tumor proliferation. Mechanistic study found that inflammation-related factors cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were highly elevated by pretreatment with capsaicin, suggesting an inflammation-dependent mechanism. Furthermore, mice that were administered capsaicin exhibited significant up-regulation of phosphorylation of nuclear factor kappaB (NF-kappa B), Erk and p38 but had no effect on JNK. Thus, our results indicated that inflammation, Erk and P38 collectively played a crucial role in cancer-promoting effect of capsaicin on carcinogen-induced skin cancer in mice. (C) 2015 Elsevier Ltd. All rights reserved.
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