Mohan Shankar , G. and Vijai , Alex V and Amrutha, Nisthul A. and Archana , Retnakumari P and Ruby , John Anto (2019) Pre‐clinical evidences for the efficacy of tryptanthrin as a potent suppressor of skin cancer. Cell Proliferation. ISSN 1365-2184

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Abstract

Objective: Clinical trials have demonstrated the efficacy of indigo naturalis, a traditional Chinese medicine ingredient, against psoriasis, a skin disease characterized by keratinocyte hyperproliferation and inflammation. The present study investigates the efficacy of tryptanthrin, a bioactive compound in indigo naturalis, against nonmelanoma skin cancer (NMSC) and the signalling events involved. Methods: Efficacy of tryptanthrin against NMSC was assessed using DMBA/PMAinduced skin carcinogenesis model in Swiss albino mice. Immunostaining for PCNA and ki‐67 was used to mark proliferating cells in tissues. Haematoxylin and eosin staining and toluidine staining were employed to assess inflammation, and TUNEL assay was used to detect apoptosis in tissues. The signalling events were evaluated using Western blot, imunohistochemistry and immunofluorescence staining. MTT assay and clonogenic assay were performed to assess the viability and proliferation of cancer cells, in vitro. Results: In mice, topical application of tryptanthrin suppressed skin carcinogenesis. It attenuated inflammation, impeded the proliferation of hair follicle (HF) cells and suppressed the activation of β‐catenin, a major driver of HF cell proliferation. Additionally tryptanthrin suppressed the activation of ERK1/2 and p38, both of which promote β‐ catenin activation and lowered the expression of c‐Myc and cyclin‐D1. Tryptanthrin suppressed the proliferation of the human NMSC cell line, A431 and abrogated EGFinduced activation of β‐catenin and subsequent cytoskeletal rearrangement. Conclusion: The study demonstrates with molecular evidence that tryptanthrin is an effective suppressor of NMSC.

Item Type:	Article
Uncontrolled Keywords:	Tryptanthrin; multistage carcinogenesis model; pre-clinical study; skin cancer
Subjects:	Cancer Research
Depositing User:	Central Library RGCB
Date Deposited:	13 Dec 2019 11:46
Last Modified:	06 Jan 2020 09:19
URI:	http://rgcb.sciencecentral.in/id/eprint/907

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