Lupeol, a triterpene, inhibits early responses of tumor promotion induced by benzoyl peroxide in murine skin

The modulating effect of Lupeol [lup-20(29)-en-3 beta -ol], a triterpene fo und in many fruits and medicinal plants, on benzoyl peroxide-induced tumor promotion responses or tumor promotion in murine skin is described. Benzoyl peroxide is an effective cutaneous tumor promoter acting through the gener ation of oxidative stress, the induction of ornithine decarboxylase activit y and the enhancement of DNA synthesis. Benzoyl peroxide treatment increase s cutaneous microsomal lipid pel-oxidation and hydrogen peroxide generation . The activity of the cutaneous antioxidant enzymes, namely catalase, gluta thione peroxidase, glutathione reductase and glutathione S-transferase, is decreased and levels of cutaneous glutathione are depleted. Benzoyl peroxid e treatment also induces ornithine decarboxylase activity and enhances [H-3 ]thymidine uptake in DNA synthesis. Prophylactic treatment of mice with lup eol (0.75 and 1.5 mg per animal) 1 hour before benzoyl peroxide treatment r esulted in a diminution of benzoyl peroxide-mediated damage. The susceptibi lity of cutaneous microsomal membrane to lipid pel-oxidation and hydrogen p eroxide generation was significantly reduced (P < 0.01 and P < 0.01, respec tively). In addition, depleted levels of glutathione and inhibited activity of antioxidant enzymes were recovered to a significant level (P<0.01, P<0. 05 and Pc 0.01, respectively). Similarly, the elevated ornithine decarboxyl ase activity and enhanced thymidine uptake in DNA synthesis were inhibited significantly (P <0.05) in a dose-dependent manner. The protective effect o f lupeol was dose dependent in all parameters. The results suggest that lup eol is an effective skin chemopreventive agent that may suppress benzoyl pe roxide-induced cutaneous toxicity. (C) 2001 Academic Press.