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Silibinin Inhibits Ultraviolet B Radiation-Induced Mast Cells Recruitment and Bone Morphogenetic Protein 2 Expression in the Skin at Early Stages in Ptch(+/-) Mouse Model of Basal Cell Carcinoma

Silibinin Inhibits Ultraviolet B Radiation-Induced Mast Cells Recruitment and Bone Morphogenetic Protein 2 Expression in the Skin at Early Stages in Ptch(+/-) Mouse Model of Basal Cell Carcinoma

Cindy Rigby, Gagan Deep, Anil Jain, David J Orlicky, Chapla Agarwal, Rajesh Agarwal

Mol Carcinog. 2019 Jul;58(7):1260-1271.

PMID: 30912211

Abstract:

Around 80% of nonmelanoma skin cancers (NMSCs) are basal cell carcinoma (BCC), still studies evaluating the efficacy of chemopreventive agents during early stage/s of BCC development are lacking. Accordingly, utilizing the well-established patched (Ptch)+/- mouse model of ultraviolet B (UVB) radiation-induced BCC formation, we excised skin samples from UVB exposed Ptch+/- and Ptch+/+ mice before tumor formation to study the promotion/progression of BCC and to determine the efficacy and target/s of silibinin, a well-known skin cancer chemopreventive agent. UVB exposure for 1 month increased the number of mast cells in Ptch+/- mice by ~48% (P < 0.05), which was completely inhibited by silibinin. Polymerase chain reaction profiler array analysis of skin samples showed strong molecular differences between Ptch+/+ and Ptch+/- mice which were either unexposed or UVB irradiated+/- silibinin treatment. Most notably, silibinin treatment significant decreased the expression of BMP-2, Bbc3, PUMA, and Ccnd1 in Ptch+/- mice irradiated with silibinin + UVB. Additional studies showed that silibinin targets UVB-induced expression of bone morphogenetic protein 2 (BMP-2) in Ptch+/- mouse skin. Last, our studies found that silibinin strongly attenuates UVB-induced BMP-2 expression and DNA damage in Ptch+/- mouse skin ex vivo only after single UVB exposure. Together, our results suggest a possible role of mast cell recruitment and BMP-2 activation in the early stages of BCC development; these are strongly inhibited by silibinin suggesting its possible chemopreventive efficacy against BCC formation in long-term UVB exposure regimen.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP142796245	2,3-Dehydrosilybin B		142796-24-5	Price

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