Effects of Magnolol on UVB-induced Skin Cancer Development in Mice and its Possible Mechanism of Action
Menée in vitro et in vivo à l'aide d'un modèle murin, cette étude évalue les effets chimiopréventifs du magnolol, une substance extraite de l'écorce et du fruit du Magnolia, sur un cancer de la peau induit par les rayonnements ultraviolets B
BACKGROUND:Magnolol, a plant lignan isolated from the bark and seed cones of Magnolia officinalis, has been shown to have chemopreventive effects on chemically-induced skin cancer development. The objectives of this investigation are to study anticarcinogenic effects of magnolol on UVB-induced skin tumor development in SKH-1 mice, a model relevant to humans, and determine possible role of apoptosis and cell cycle arrest involved in the skin tumor development.METHODS:UVB- induced complete carcinogenesis model in SKH-1 mice was used for determining the preventive effects of magnolol on skin cancer development. Western blotings and flow cytometric analysis were used to study the effects of magnolol on apoptosis and cell cycle.RESULTS:Magnolol pretreated groups (30, 45, 60 ug) before UVB treatments (30 mJ/cm2, 5 days/week) resulted in 27- 55 % reduction in tumor multiplicity as compared to control group. Magnolol pretreatement increased the expression of cleaved caspase-8 and poly-(-ADP-ribose) polymerase (PARP) and decreased expression of proteins involved in G2/Mphase of cell cycle and increased expression of p21, a cell cycle inhibitor in skin samples from SKH-1 mice. Treatment of A431 cells with magnolol decreased cell viability and cell proliferation in a concentration dependant manner. Magnolol induced G2/M phase cell cycle arrest in A431 cells at 12 h with decreased expression of cell cycle proteins such as cyclin B1, cyclin A, CDK4, Cdc2 and simultaneous increase in expression of Cip/p21, a cyclin-dependent kinase inhibitor. Magnolol induced apoptosis in vivo and in vitro with an increased expression of caspase-8 and cleaved PARP. Phosho-signal trasducers and activators of transcription 3 (Tyr705) and B-Raf, MEK and AKT were down regulated whereas phosphorylation of ERK was induced by magnolol. CONCLUSIONS:Magnolol pretreatments prevent UVB- induced skin cancer development by enhancing apoptosis and causing cell cycle arrest at G2/M phase, and affecting various signaling pathways. Magnolol could be a potentially safe and potent anticarcinogenic agent for skin cancer.