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.
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http://dx.doi.org/10.1038/srep11107 | DOI Listing |
Int Ophthalmol
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Department of Ophthalmology, Staedtisches Klinikum Dessau, Brandenburg Medical School Theodor Fontane, Dessau, Germany.
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Ophthalmology
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Casey Eye Institute, Cornea Division, Oregon Health & Science University, Portland, Oregon.
J Invest Dermatol
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Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China; National Engineering Research Center of Personalized Diagnostic and Therapeutic Technology, Changsha, China; Furong Laboratory, Changsha, China; Hunan Key Laboratory of Skin Cancer and Psoriasis, Hunan Engineering Research Center of Skin Health and Disease, Xiangya Hospital, Central South University, Changsha, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, China. Electronic address:
Melanoma is a devastating form of skin cancer characterized by a high mutational burden, limited treatment success, and dismal prognosis. Although immunotherapy and targeted therapies have significantly revolutionized melanoma treatment, the majority of patients fail to achieve durable responses, highlighting the urgent need for novel therapeutic strategies. Ferroptosis, an iron-dependent form of regulated cell death driven by the overwhelming accumulation of lipid peroxides, has emerged as a promising therapeutic approach in preclinical melanoma models.
View Article and Find Full Text PDFJ Am Chem Soc
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Department of Pharmacy, The First Affiliated Hospital of USTC; Division of Life Sciences and Medicine, University of Science and Technology of China, Anhui Provincial Key Laboratory of Precision Pharmaceutical Preparation and Clinical Pharmacy, Hefei, Anhui 230026, China.
Inhibitors of the PD-1/PD-L1 immune checkpoint have revolutionized cancer treatment. However, the clinical response remains limited, with only 20% of patients benefiting from treatment and approximately 60% of PD-L1-positive patients exhibiting resistance. One key factor contributing to resistance is the externalization of phosphatidylserine (PS) on the surface of cancer cells, which suppresses immune responses and promotes PD-L1 expression, further hindering the efficacy of PD-L1 blockade therapies.
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