Pre‐clinical evidences for the efficacy of tryptanthrin as a potent suppressor of skin cancer

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 non‐melanoma skin cancer (NMSC) and the signalling events involved. Methods Efficacy of tryptanthrin against NMSC was assessed using DMBA/PMA‐induced 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 EGF‐induced activation of β‐catenin and subsequent cytoskeletal rearrangement. Conclusion The study demonstrates with molecular evidence that tryptanthrin is an effective suppressor of NMSC.

Isatis tinctoria L. (Woad): A Review of Its Botany, Ethnobotanical Uses, Phytochemistry, Biological Activities, and Biotechnological Studies

“…Recently, tryptanthrin has also been shown to be an effective suppressor of non-melanoma skin cancer (NMSC), as demonstrated by using dimethylbenz[a]anthracene/phorbol 12myristate 13acetate (DMBA/PMA) induced skin carcinogenesis model in Swiss albino mice [79]. It was found that the compound disrupted DMBA/PMA-induced expansion of hair follicle cells by suppressing the activation of β-catenin, which is a major driver of hair follicle cell proliferation.…”

Experimental research in topical psoriasis therapy (Review)

“…The first search was made in order to assess the scientific interest in the topic. The second search had the following steps: Introduction of words and limits in PubMed with first step exclusion criteria for articles that did not refer to a potential substance for topical therapy, formulas from traditional medicine that did not specify the active ingredient (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). The second step exclusion criterion was if the substance of interest was not administered topically.…”

A Comprehensive Review of the Chemistry, Pharmacokinetics, Pharmacology, Clinical Applications, Adverse Events, and Quality Control of Indigo Naturalis

“…Tryptanthrin could significantly reduce the size and multiplicity of skin tumors. In addition, tryptanthrin impeded the diffusion of hair follicle cells by interfering with the activity of β-catenin and inhibited A431 cells by abolishing the activation of β-catenin (Shankar et al, 2019). Moreover, the oxygen atom at position 6 of the tryptanthrin ring was coupled to heme iron of tryptophan 2,3-dioxygenase, which was a therapeutic target in cancer diseases, via coordination interaction and thus exhibited higher tryptophan 2,3-dioxygenase inhibitory activity (Zhang et al, 2018).…”