Abstract 5271: Inhibition of ultraviolet B radiation-induced mast cell recruitment by silibinin in its efficacy against basal cell carcinoma in Ptch+/− mouse model
Authors: Paudel Sandeep , Mishra Neha , Raina Komal , Agarwal Chapla , Agarwal Rajesh 
Published: April 2023

Abstract
Recently, we have reported the chemopreventive and therapeutic efficacy of topical silibinin (SB, a natural flavonolignan from milk thistle seeds) application against ultraviolet B radiation (UVB)-induced basal cell carcinoma (BCC) growth and progression. During the histopathological analyses of the skin tissues in these studies, we observed a significant decrease in mast cell (MC) numbers in SB-treated UVB-exposed groups. Although, the MCs are primarily responsible for conferring protection against diseases and pathogens, the dynamics of BCC and MCs are complex, where MCs may also contribute to tumor transformation/progression; furthermore, their role in BCC is poorly understood. To address this gap, we first assessed the course of MC recruitment in wild-type (C57BL/6) mice vs. Ptch+/− mice as a function of time following either a single or thrice weekly UVB (240 mJ/cm2) exposure. Results indicated that Ptch+/− mice had significantly higher infiltration of MCs compared to C57BL/6 mice. MC infiltration into the epidermis/dermis was initiated as early as 30 min post single UVB exposure in Ptch+/− mice, and the MCs remained in the epidermis/dermis for a longer duration in the Ptch+/− mice compared to C57BL/6 mice. Next, the effect of SB treatment (topical-9 mg/200 µl acetone) on MC recruitment upon UVB exposure in these mice was assessed. Notably, SB treatment significantly decreased MC numbers in both pre- and post-UVB single exposure by ~48% and ~43%, respectively, and in multiple exposure by ~55% and ~41%, respectively. Furthermore, UVB exposure for 26 and/or 46 weeks caused an increase in MC numbers by ~2.3 fold in BCC tumors, which was also decreased by both pre- (~38-39%) and post- (~20-26%) SB treatments at 26 and 46 weeks, respectively. Notably, in preformed BCC tumors (UVB 26 weeks exposure), SB treatment for 20 weeks post UVB stoppage also decreased the number of MCs by ~25%. Thus, it was evident that anti-BCC efficacy of SB was associated with its potential to decrease MC numbers. To further understand the role of SB in MC regulation, assessment of cell viability and migration (towards BCC cell lines) in in vitro assays were performed with/without SB exposure in bone marrow derived mast cells (BMMCs from C57BL/6 mice), which indicated that non-toxic doses of SB (25 -100 µM) at the 48-72 h timepoint were able to inhibit BMMC migration towards BCC cell lines. Furthermore, a correlation of other immune cells (T cells, macrophages, etc.) with MC recruitment and anti-BCC effect was also determined. Taken together, our results suggest that SB effectively regulates MC numbers/function in its efficacy against BCC in Ptch+/− mouse model; thus, further in depth-studies, deciphering the associated molecular pathways, could yield novel preventive/therapeutic avenues targeting MCs in BCC and other cancers.
Citation Format: Sandeep Paudel, Neha Mishra, Komal Raina, Chapla Agarwal, Rajesh Agarwal. Inhibition of ultraviolet B radiation-induced mast cell recruitment by silibinin in its efficacy against basal cell carcinoma in Ptch+/− mouse model. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5271.