Promoting effect of Se-allylselenocysteine on 7,12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin tumorigenesis

Se-allylselenocysteine (ASC), an analogue of garlic bioactive compound, has been shown to inhibit mammary carcinogenesis in vivo and cell growth in vitro. However, the function of ASC on anti-inflammatory effects remains largely unknown. Therefore, we investigated whether ASC has an anti-inflammatory effect on lipopolysaccharide (LPS)-induced inflammation or an anti-tumor effect promoting on DMBA/TPA-induced skin tumorigenesis and tried to elucidate the mechanisms involved. Herein, the results showed that ASC inhibited LPS-induced production of nitric oxide (NO) with a decreased protein level of inducible nitric oxide synthase (iNOS) in RAW 264.7 cells. However, ASC enhanced LPS-induced cyclooxygenase-2 (COX-2) protein levels and mRNA expression. Interestingly, we found for the first time that topical application of ASC on the dorsal skin of DMBA-initiated and TPA-promoted mice significantly accelerated skin tumorigenesis and raised tumor multiplicity as compared to the positive control group (DMBA/TPA). The number of tumours that were 1–3, 3–5, and > 5 mm in size per mouse increased in a dose-dependent manner in the ASC pre-treated groups. Pre-treatment with ASC showed a significant increase in the expression of COX-2 compared with the positive control group. Thus, ASC may modulate the COX-2 protein expression and promote DMBA/TPA-induced skin cancer in mice.