Prophylaxis of Diallyl Disulfide on Skin Carcinogenic Model Via P21-dependent Nrf2 Stabilization

Overview

Journal Sci Rep

Specialty Science

Date 2016 Oct 21

PMID 27759091

Citations 20

Authors

Yunlong Shan

Zhonghong Wei

Li Tao

Siliang Wang

Feng Zhang

Cunsi Shen

Hongyan Wu

Zhaoguo Liu

Pingting Zhu

Aiyun Wang

Wenxing Chen

Yin Lu

Affiliations

Soon will be listed here.

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.

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