DW-F5: A novel formulation against malignant melanoma from Wrightia tinctoria.

Jayesh Antony,Elizabeth Jayex Panakkal,Sophia Ran,Sankar S,Harsha Chandran,Sophia Margaret Joseph,Nishanth Kumar S,Shabna A,Anju Paul,Vinod V,Sridivya I V,Ruby John Anto,Lekshmi R Nath,M.S.R Murty,Sriramya I V,Minakshi Saikia,Mohana Rao Katiki,Easwary Rajan

doi:10.1038/srep11107

Abstract

Wrightia tinctoria is a constituent of several ayurvedic preparations against skin disorders including psoriasis and herpes, though not yet has been explored for anticancer potential. Herein, for the first time, we report the significant anticancer properties of a semi-purified fraction, DW-F5, from the dichloromethane extract of W. tinctoria leaves against malignant melanoma. DW-F5 exhibited anti-melanoma activities, preventing metastasis and angiogenesis in NOD-SCID mice, while being non-toxic in vivo. The major pathways in melanoma signaling mediated through BRAF, WNT/β-catenin and Akt-NF-κB converging in MITF-M, the master regulator of melanomagenesis, were inhibited by DW-F5, leading to complete abolition of MITF-M. Purification of DW-F5 led to the isolation of two cytotoxic components, one being tryptanthrin and the other being an unidentified aliphatic fraction. The overall study predicts Wrightia tinctoria as a candidate plant to be further explored for anticancer properties and DW-F5 as a forthcoming drug formulation to be evaluated as a chemotherapeutic agent against malignant melanoma.

Highlights

Wrightia tinctoria is a constituent of several ayurvedic preparations against skin disorders including psoriasis and herpes, though not yet has been explored for anticancer potential
We report the anti-melanoma efficacy of a semi- purified fraction (DW-F5) isolated from Wrightia tinctoria (Roxb.) R.Br., a small medicinal tree native to India and Burma and is known in Siddha and Ayurvedic system of Indian traditional medicine as a cure for various skin related ailments. Different parts of this plant have been accredited for alleviating diseases such as psoriasis and herpes[1,2] and for the preparation of hair oils used for treating various scalp and skin disorders[1,3]
No scientific study has been reported on the anti-cancer activity of this plant except some anecdotal information regarding its use as a traditional remedy for curing lung and breast cancer, which is not validated through scrupulous scientific experiments or systematic studies[8]

Summary

Introduction

Wrightia tinctoria is a constituent of several ayurvedic preparations against skin disorders including psoriasis and herpes, though not yet has been explored for anticancer potential. We report the anti-melanoma efficacy of a semi- purified fraction (DW-F5) isolated from Wrightia tinctoria (Roxb.) R.Br., a small medicinal tree native to India and Burma and is known in Siddha and Ayurvedic system of Indian traditional medicine as a cure for various skin related ailments. Different parts of this plant have been accredited for alleviating diseases such as psoriasis and herpes[1,2] and for the preparation of hair oils used for treating various scalp and skin disorders[1,3]. This study demonstrates the promising effects of DW-F5 in blocking the melanoma growth both in vitro and in vivo along with its efficacy in modulating signals known to play a crux role in melanoma progression

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Results

Conclusion