Diallyl sulfide protects against ultraviolet B-induced skin cancers in SKH-1 hairless mouse: analysis of early molecular events in carcinogenesis

Abstract

Background: Diallyl sulfide (DAS) has been shown to have a preventive effect against various cancers.

Aims and objectives: We evaluated the protective effects of DAS in regression of ultraviolet B (UVB)-induced skin tumor formation in SKH-1 hairless mice and its underlying early molecular biomarkers.

Methods: We examined the efficacy of DAS in UVB light-induced skin lesion in SKH-1 hairless mice and the associated molecular events.

Results: Mice irradiated with UVB at 180mJ/cm(2) twice per week elicited 100% tumor incidence at 20 weeks. The topical application of DAS before UVB irradiation caused a delay in tumor appearance, multiplicity, and size. The topical application of DAS before and immediately after a single UVB irradiation (180mJ/cm(2) ) resulted in a significant decrease in UVB-induced thymine dimer-positive cells, expression of proliferative cell nuclear antigen (PCNA), terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, and apoptotic sunburn cells, together with an increase in p53 and p21/Cip1-positive cell population in the epidermis. Simultaneously, DAS also significantly inhibited nuclear factor-κB (NF-κB), cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and nitric oxide (NO) levels.

Conclusions: The protective effect of DAS against photocarcinogenesis is accompanied by the down-regulation of cell-proliferative controls, involving thymine dimer, PCNA, apoptosis, transcription factors NF-κB, and of inflammatory responses involving COX-2, PGE2, and NO, and up-regulation of p53, p21/Cip1 to prevent DNA damage and facilitate DNA repair.