title: Prophylaxis of Diallyl Disulfide on Skin Carcinogenic Model via p21-dependent Nrf2 stabilization.
abstract: Cancer prevention through intake of biologically active natural products appears to be an accessible way to reduce the risk of cancer. Diallyl disulfide (DADS), a major garlic derivative, has exhibited potential role in cancer therapy. The study is aimed to evaluate the prophylactic effect of DADS in chemically induced mouse skin carcinogenesis and investigate the molecular targets mediated by DADS. Two-stage chemically induced carcinogenesis model by cutaneous application of DMBA and subsequent TPA was established to study the prophylactic effect of DADS. As a result, we observed that DADS dose-dependently attenuated skin tumor incidence and multiplicity in the model mice, which was related to the up-regulation of a bunch of antioxidant enzymes activities and the nuclear accumulation of Nrf2. Furthermore, we developed skin carcinogenesis in Nrf2 knockout mice which could reverse the activity of DADS. Finally, we uncovered the underlying mechanism that DADS promoted the endogenous interaction between p21 and Nrf2, which was critical for impairing the Keap1-mediated degradation of Nrf2. Based on the results, we concluded that DADS was a promising cancer chemoprevention agent and suggested a garlic-rich diet might be beneficial to reduce the cancer risk in our daily life.
authors.affiliation: Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Yunlong
authors.initials: Y
authors.lastname: Shan
authors.affiliation: Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Zhonghong
authors.initials: Z
authors.lastname: Wei
authors.affiliation: Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Li
authors.initials: L
authors.lastname: Tao
authors.affiliation: Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Siliang
authors.initials: S
authors.lastname: Wang
authors.affiliation: Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Cunsi
authors.initials: C
authors.lastname: Shen
authors.affiliation: Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Wu
authors.affiliation: Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Zhaoguo
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Pingting
authors.initials: P
authors.lastname: Zhu
authors.affiliation: Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.|Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine (TCM) Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Aiyun
authors.initials: A
authors.lastname: Wang
authors.affiliation: Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.|Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine (TCM) Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Wenxing
authors.initials: W
authors.lastname: Chen
authors.affiliation: Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.|Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine (TCM) Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Lu
mesh_terms: D000498:Allyl Compounds / Q000008:administration & dosage*; D000818:Animals; D000959:Antihypertensive Agents; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D018890:Chemoprevention / Q000379:methods*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D004195:Disease Models, Animal; D004220:Disulfides / Q000008:administration & dosage*; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D012878:Skin Neoplasms / Q000139:chemically induced / Q000517:prevention & control*
chemical_list: D000498:Allyl Compounds; D000959:Antihypertensive Agents; D000970:Antineoplastic Agents; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004220:Disulfides; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; C028009:diallyl disulfide