title: Cancer-promoting effect of capsaicin on DMBA/TPA-induced skin tumorigenesis by modulating inflammation, Erk and p38 in mice.
abstract: 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-κB), 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.
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China.
authors.forename: Zhaoguo
authors.initials: Z
authors.lastname: Liu
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China; Medical College of Yangzhou University, Yangzhou 225001, Jiangsu Province, China.
authors.forename: Pingting
authors.initials: P
authors.lastname: Zhu
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Tao
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China; Jiangsu Key Laboratory of Pediatric Respiratory Disease, Nanjing 210023, Jiangsu Province, China.
authors.forename: Cunsi
authors.initials: C
authors.lastname: Shen
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China.
authors.forename: Siliang
authors.initials: S
authors.lastname: Wang
authors.affiliation: Jiangsu Province Hospital of TCM, Nanjing 210029, Jiangsu Province, China.
authors.forename: Lingang
authors.initials: L
authors.lastname: Zhao
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Wu
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China.
authors.forename: Fangtian
authors.initials: F
authors.lastname: Fan
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Lin
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China.
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China.
authors.forename: Zhonghong
authors.initials: Z
authors.lastname: Wei
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Sun
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Liu
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China; Jiangsu Province Hospital of TCM, Nanjing 210029, Jiangsu Province, China.
authors.forename: Aiyun
authors.initials: A
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China; Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, Nanjing 210023, Jiangsu Province, China. Electronic address: profyinlu@163.com.
authors.forename: Yin
authors.initials: Y
authors.lastname: Lu
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000009:adverse effects*; D000818:Animals; D002211:Capsaicin / Q000009:adverse effects*; D063646:Carcinogenesis / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D005260:Female; D006965:Hyperplasia / Q000139:chemically induced / Q000473:pathology; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D012867:Skin / Q000187:drug effects; D012878:Skin Neoplasms / Q000139:chemically induced*; D013755:Tetradecanoylphorbol Acetate / Q000009:adverse effects*; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D015127:9,10-Dimethyl-1,2-benzanthracene; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D013755:Tetradecanoylphorbol Acetate; D002211:Capsaicin
keywords: COX-2; Capsaicin; DMBA/TPA; Skin inflammation; Tumorigenesis; iNOS