Chemopreventive effects of honokiol on UVB-induced skin cancer development.

摘要

BACKGROUND: Skin cancer is the most prevalent of all cancer types and its incidence is expected to increase substantially. Chemoprevention involves the administration of chemical agents to prevent initiation, promotion and/or progression that occurs during neoplastic development. Honokiol, a plant lignan isolated from bark and seed cones of Magnolia officinalis, has been shown to have chemopreventive effects on chemically induced skin cancer development. Aim: The objective of this investigation was to study the chemopreventive effects of honokiol on UVB-induced skin tumor development in SKH-1 mice, a model relevant to humans, and to elucidate the possible role of apoptotic proteins involved in the prevention of skin tumor development. MATERIALS AND METHODS: Female SKH-1 mice were divided into two groups. Group 1 received acetone (0.2 ml, topical) and Group 2 received honokiol (30 microg in 0.2 ml acetone, topical) one hour before UVB treatment. Tumor initiation and promotion were carried out by UVB radiation (30 mJ/cm(2)/day), 5 days a week for 30 weeks. Tumor counts and mouse weights were taken weekly. RESULTS: The honokiol-pretreated group exhibited a 45% reduction in tumor multiplicity as compared to the control group. Mechanistic studies showed the possible involvement of caspase-3, caspase-8, caspase-9, poly (ADP-ribose) polymerase (PARP) and p53 activation (p<0.05) leading to the induction of DNA fragmentation and apoptosis. CONCLUSION: Pretreatment with honokiol, at concentrations in micrograms per application compared with milligram applications of other potential chemopreventive agents, prevents UVB-induced skin cancer development, possibly by activating proapoptotic proteins through both intrinsic and extrinsic pathways.