title: DW-F5: A novel formulation against malignant melanoma from Wrightia tinctoria.
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.
authors.affiliation: Division of Cancer Research, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram 695 014, Kerala, India.
authors.forename: Jayesh
authors.initials: J
authors.lastname: Antony
authors.affiliation: Division of Cancer Research, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram 695 014, Kerala, India.
authors.forename: Minakshi
authors.initials: M
authors.lastname: Saikia
authors.affiliation: Division of Cancer Research, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram 695 014, Kerala, India.
authors.forename: V
authors.initials: V
authors.lastname: Vinod
authors.affiliation: Division of Cancer Research, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram 695 014, Kerala, India.
authors.forename: Lekshmi R
authors.initials: LR
authors.lastname: Nath
authors.affiliation: Medicinal Chemistry and Pharmacology Division, Indian Institute of Chemical Technology, Hyderabad 500007, India.
authors.forename: Mohana Rao
authors.initials: MR
authors.lastname: Katiki
authors.affiliation: Medicinal Chemistry and Pharmacology Division, Indian Institute of Chemical Technology, Hyderabad 500007, India.
authors.forename: M S R
authors.initials: MS
authors.lastname: Murty
authors.affiliation: Division of Cancer Research, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram 695 014, Kerala, India.
authors.forename: Anju
authors.initials: A
authors.lastname: Paul
authors.affiliation: Division of Cancer Research, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram 695 014, Kerala, India.
authors.forename: A
authors.initials: A
authors.lastname: Shabna
authors.affiliation: Division of Cancer Research, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram 695 014, Kerala, India.
authors.forename: Harsha
authors.initials: H
authors.lastname: Chandran
authors.affiliation: Division of Cancer Research, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram 695 014, Kerala, India.
authors.forename: Sophia Margaret
authors.initials: SM
authors.lastname: Joseph
authors.affiliation: Agroprocessing and Natural Products Division, National Institute for Interdisciplinary Science and Technology (NIIST), Council of Scientific and Industrial Research (CSIR), Thiruvanathapuram 695 019, Kerala, India.
authors.forename: Kumar S
authors.initials: KS
authors.lastname: Nishanth
authors.affiliation: Division of Cancer Research, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram 695 014, Kerala, India.
authors.forename: Elizabeth Jayex
authors.initials: EJ
authors.lastname: Panakkal
authors.affiliation: Division of Cancer Research, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram 695 014, Kerala, India.
authors.forename: I  V
authors.initials: I
authors.lastname: Sriramya
authors.affiliation: Division of Cancer Research, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram 695 014, Kerala, India.
authors.forename: I  V
authors.initials: I
authors.lastname: Sridivya
authors.affiliation: Department of Medical Microbiology, Immunology and Cell Biology, Southern Illinois University-School of Medicine, P.O. Box 19626, Springfield, Illinois, USA.
authors.forename: Sophia
authors.initials: S
authors.lastname: Ran
authors.affiliation: Department of Pathology, Government Medical College, Thiruvananthapuram 695 011, Kerala, India.
authors.forename: S
authors.initials: S
authors.lastname: Sankar
authors.affiliation: Department of Chemistry, Sree Kerala Varma College, Thrissur 680011, Kerala, India.
authors.forename: Easwary
authors.initials: E
authors.lastname: Rajan
authors.affiliation: Division of Cancer Research, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram 695 014, Kerala, India.
authors.forename: Ruby John
authors.initials: RJ
authors.lastname: Anto
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D029062:Apocynaceae / Q000737:chemistry*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D004195:Disease Models, Animal; D006801:Humans; D008545:Melanoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D010936:Plant Extracts / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D011799:Quinazolines / Q000737:chemistry / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D011799:Quinazolines; C046243:tryptanthrine