Inhibitory effect of a flavonoid antioxidant silymarin on benzoyl peroxide-induced tumor promotion, oxidative stress and inflammatory responses in SENCAR mouse skin.
In this communication, we investigate the preventive effect of a flavonoid antioxidant, silymarin, on free radical-generating skin tumor promoting agent benzoyl peroxide (BPO)-induced tumor promotion, oxidative stress and inflammatory responses in SENCAR mouse skin. Topical application of silymarin at a dose of 6 mg prior to BPO resulted in a highly significant protection against BPO-induced tumor promotion in 7,12-dimethylbenz[a]anthracene-initiated SENCAR mouse skin. The preventive effect of silymarin was evident in terms of a 70% reduction (P < 0.001) in tumor incidence, a 67% reduction (P < 0.001) in tumor multiplicity and a 44% decrease (P < 0.001) in tumor volume/tumor. In oxidative stress studies, topical application of BPO resulted in 75, 87 and 61% depletion in superoxide dismutase (SOD), catalase and glutathione peroxidase (GPX) activities in mouse epidermis, respectively. These decreases in antioxidant enzyme activities were significantly (P < 0.005-0.001) reversed by pre-application of silymarin in a dose-dependent manner. The observed effects of silymarin were 18-66, 32-72 and 20-67% protection against BPO-induced depletion of SOD, catalase and GPX activity in mouse epidermis, respectively. Silymarin pre-treatment also resulted in a dose-dependent inhibition (35-87%, P < 0.05-0. 001) of BPO-induced lipid peroxidation in mouse epidermis. In inflammatory response studies, silymarin showed a strong inhibition of BPO-induced skin edema (62-85% inhibition, P < 0.001), myeloperoxidase activity (42-100% inhibition, P < 0.001) and interleukin-1alpha protein level in epidermis (36-81% inhibition, P < 0.001). These results, together with our other recent studies, suggest that silymarin could be useful in preventing a wide range of carcinogen and tumor promoter-induced cancers.
Zhao
J
J
Center for Cancer Causation and Prevention, AMC Cancer Research Center, Denver, CO 80214, USA.
Lahiri-Chatterjee
M
M
Sharma
Y
Y
Agarwal
R
R
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D001585:Benzoyl Peroxide / Q000633:toxicity*; D005260:Female; D007375:Interleukin-1 / Q000502:physiology; D015227:Lipid Peroxidation / Q000187:drug effects; D051379:Mice; D018632:Mice, Inbred SENCAR; D018384:Oxidative Stress; D012838:Silymarin / Q000494:pharmacology*; D012878:Skin Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D013482:Superoxide Dismutase / Q000378:metabolism
D016588:Anticarcinogenic Agents; D000975:Antioxidants; D007375:Interleukin-1; D012838:Silymarin; D013482:Superoxide Dismutase; D001585:Benzoyl Peroxide