β-Elemene inhibits 7,12-dimethylbenz(a)anthracene/12-O-tetradecanoylphorbol-13-acetate-induced skin tumorigenesis through suppression of NF-κB-associated signaling events in the mouse skin model

β-Elemene (1-methyl-1-vinyl-2,4-diisopropenyl-cyclohexane), a natural sesquiterpene-derived curcumae radix, exhibits a variety of pharmacologic properties including anticancer. However, the molecular action of β-elemene in chemical-induced skin carcinogenesis remains unclear. Therefore, the present study executes to investigate a possible effect of β-elemene in the 7,12-dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted skin tumor model. The experimental mice were subjected to execute two-stage skin carcinogenesis and it has been initiated by the addition of DMBA on the dorsal portion of the mouse skin. One week after, for chemical carcinogen of mice, topical exposure of DMBA has been induced following with TPA (5 nmol) in acetone (200 μL) given weekly twice for 20 weeks respectively. After completion of the experimental period, we noticed that 100% of tumor incidence, histopathological changes, decreased lipid peroxidation (LPO), and decreased antioxidant levels in DMBA/TPA-promoted skin carcinogenesis. Furthermore, enhanced activity of inflammatory protein markers (nuclear factor [NF]-κB, tumor necrosis factor-α, interleukin-6, cyclooxygenase-2, and nitric oxide synthase) and cell-proliferative messenger RNA markers (PCNA, cyclin D1), and increased antiapoptotic protein Bcl-2; decreased proapoptotic protein marker events Bax and caspase 3 and 9 expressions were noticed in DMBA/TPA promoted skin tissue. In this study, we noticed that β-elemene noticeably reversed the histopathological changes and antioxidant levels in tumor-bearing mice. Conversely, β-elemene effectively inhibits inflammation, cell proliferation events, and enhances proapoptotic factors, by suppression of NF-κB transcriptional activation in DMBA/TPA animals. Thus, we concluded that β-elemene prevents DMBA/TPA promoted skin carcinogenesis through its antioxidant and abate inflammation markers and cell-proliferative markers also activating proapoptotic molecules.

Keywords: 12-O-tetradecanoylphorbol-13-acetate; antioxidant; apoptosis; proliferation; β-elemene.