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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
Author(s) -
Rigby Cindy,
Deep Gagan,
Jain Anil,
Orlicky David J.,
Agarwal Chapla,
Agarwal Rajesh
Publication year - 2019
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.23008
Subject(s) - silibinin , biology , cancer research , patched , skin cancer , pharmacology , hedgehog signaling pathway , cancer , microbiology and biotechnology , signal transduction , genetics
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.