1. A novel stilbene-like compound that inhibits melanoma growth by regulating melanocyte differentiation and proliferation
- Author
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Cheng-chen Huang, Sheng-Ping L. Hwang, Nicholas M. Schlaeger, Aaron Monte, and Noah A. Stueven
- Subjects
0301 basic medicine ,MAPK/ERK pathway ,Skin Neoplasms ,Melanoma, Experimental ,Mitosis ,Antineoplastic Agents ,Biology ,Toxicology ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,Melanocyte differentiation ,Cell Line, Tumor ,Stilbenes ,medicine ,Animals ,Humans ,Protein kinase B ,PAX3 Transcription Factor ,Zebrafish ,Cell Proliferation ,Pharmacology ,Microphthalmia-Associated Transcription Factor ,Dose-Response Relationship, Drug ,Melanoma ,Cancer ,Cell Differentiation ,Zebrafish Proteins ,medicine.disease ,Microphthalmia-associated transcription factor ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,chemistry ,Immunology ,Cancer research ,Melanocytes ,Signal transduction ,Growth inhibition ,Mitogen-Activated Protein Kinases ,Proto-Oncogene Proteins c-akt ,Signal Transduction - Abstract
Melanoma is the most aggressive form of skin cancer. Current challenges to melanoma therapy include the adverse effects from immunobiologics, resistance to drugs targeting the MAPK pathway, intricate interaction of many signal pathways, and cancer heterogeneity. Thus combinational therapy with drugs targeting multiple signaling pathways becomes a new promising therapy. Here, we report a family of stilbene-like compounds called A11 that can inhibit melanoma growth in both melanoma-forming zebrafish embryos and mouse melanoma cells. The growth inhibition by A11 is a result of mitosis reduction but not apoptosis enhancement. Meanwhile, A11 activates both MAPK and Akt signaling pathways. Many A11-treated mouse melanoma cells exhibit morphological changes and resemble normal melanocytes. Furthermore, we found that A11 causes down-regulation of melanocyte differentiation genes, including Pax3 and MITF. Together, our results suggest that A11 could be a new melanoma therapeutic agent by inhibiting melanocyte differentiation and proliferation.
- Published
- 2017