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

• Published in: Scientific reports 2015-06, Vol.5 (1), p.11107, Article 11107
• Main Authors: Antony, Jayesh, Saikia, Minakshi, V, Vinod, Nath, Lekshmi. R., Katiki, Mohana Rao, Murty, M.S.R., Paul, Anju, A, Shabna, Chandran, Harsha, Joseph, Sophia Margaret, S, Nishanth Kumar, Panakkal, Elizabeth Jayex, V, Sriramya I., V, Sridivya I., Ran, Sophia, S, Sankar, Rajan, Easwary, Anto, Ruby John
• Format: Article
• Language: English
• Subjects: 13; 13/1; 13/106; 13/109; 13/2; 13/31; 13/51; 13/95; 14; 14/34; 59; 631/67/1813/1634; 64; 64/60; 692/699/67/1813; 82; 82/1; 82/16; 82/29; 82/51; 96; 96/1; 96/106; 96/109; 96/2; 96/63; AKT protein; Angiogenesis; Animals; Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - isolation & purification; Antineoplastic Agents, Phytogenic - pharmacology; Apocynaceae - chemistry; Apoptosis - drug effects; Cell Line, Tumor; Cell Survival - drug effects; Cell Transformation, Neoplastic - drug effects; Cytotoxicity; Dichloromethane; Disease Models, Animal; Humanities and Social Sciences; Humans; Melanoma; Melanoma - drug therapy; Melanoma - metabolism; Melanoma - pathology; Metastases; Mice, Inbred NOD; Mice, SCID; Microphthalmia-associated transcription factor; multidisciplinary; Neoplasm Metastasis; Neovascularization, Pathologic - drug therapy; Plant Extracts - pharmacology; Plant Leaves - chemistry; Psoriasis; Purification; Quinazolines - chemistry; Quinazolines - pharmacology; Science; Science (multidisciplinary); Signal Transduction - drug effects; Skin cancer; Skin diseases; Wnt protein; Xenograft Model Antitumor Assays; β-Catenin
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep11107

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.