title: Chemopreventive efficacy of menthol on carcinogen-induced cutaneous carcinoma through inhibition of inflammation and oxidative stress in mice.
abstract: Inflammation and oxidative stress have been implicated in various pathological processes including skin tumorigenesis. Skin cancer is the most common form of cancer responsible for considerable morbidity and mortality, the treatment progress of which remains slow though. Therefore, chemoprevention and other strategies are being considered. Menthol has shown high anticancer activity against various human cancers, but its effect on skin cancer has never been evaluated. We herein investigated the chemopreventive potential of menthol against 9,10-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation, oxidative stress and skin carcinogenesis in female ICR mice. Pretreatment with menthol at various doses significantly suppressed tumor formation and growth, and markedly reduced tumor incidence and volume. Moreover, menthol inhibited TPA-induced skin hyperplasia and inflammation, and significantly suppressed the expression of cyclooxygenase-2 (COX-2). Furthermore, pretreatment with menthol inhibited the formation of reactive oxygen species and affected the activities of a battery of antioxidant enzymes in the skin. The expressions of NF-κB, Erk and p38 were down-regulated by menthol administration. Thus, inflammation and oxidative stress collectively played a crucial role in the chemopreventive efficacy of menthol on the murine skin tumorigenesis.
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, China.
authors.forename: Zhaoguo
authors.initials: Z
authors.lastname: Liu
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, China.
authors.forename: Cunsi
authors.initials: C
authors.lastname: Shen
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Tao
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, China.
authors.forename: Siliang
authors.initials: S
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, China.
authors.forename: Zhonghong
authors.initials: Z
authors.lastname: Wei
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, China.
authors.forename: Yuzhu
authors.initials: Y
authors.lastname: Cao
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Wu
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, China.
authors.forename: Fangtian
authors.initials: F
authors.lastname: Fan
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Lin
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, China.
authors.forename: Yunlong
authors.initials: Y
authors.lastname: Shan
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, China.
authors.forename: Pingting
authors.initials: P
authors.lastname: Zhu
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Sun
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, China; Jiangsu Key Laboratory for Pharmacolgy and Safety Evaluation of Chinese Materia Medica, Nanjing, Jiangsu 210023, China.
authors.forename: Aiyun
authors.initials: A
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, China; Jiangsu Key Laboratory for Pharmacolgy and Safety Evaluation of Chinese Materia Medica, Nanjing, Jiangsu 210023, China.
authors.forename: Shizhong
authors.initials: S
authors.lastname: Zheng
authors.affiliation: School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, China; Jiangsu Key Laboratory for Pharmacolgy and Safety Evaluation of Chinese Materia Medica, Nanjing, Jiangsu 210023, China. Electronic address: profyinlu@163.com.
authors.forename: Yin
authors.initials: Y
authors.lastname: Lu
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000287:Administration, Topical; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D002273:Carcinogens / Q000633:toxicity; D002277:Carcinoma / Q000139:chemically induced / Q000517:prevention & control*; D018890:Chemoprevention / Q000379:methods; D051546:Cyclooxygenase 2 / Q000378:metabolism; D003872:Dermatitis / Q000517:prevention & control; D005260:Female; D005978:Glutathione / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy*; D008610:Menthol / Q000008:administration & dosage / Q000494:pharmacology*; D008813:Mice, Inbred ICR; D009374:Neoplasms, Experimental / Q000517:prevention & control; D018384:Oxidative Stress / Q000187:drug effects*; D012878:Skin Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity
chemical_list: D016588:Anticarcinogenic Agents; D002273:Carcinogens; D008610:Menthol; D015127:9,10-Dimethyl-1,2-benzanthracene; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D005978:Glutathione; D013755:Tetradecanoylphorbol Acetate
keywords: COX-2; Cancer chemoprevention; Inflammation; Menthol; Oxidative stress; Skin tumorigenesis