1. Identification of a small molecule that downregulates MITF expression and mediates antimelanoma activity in vitro
- Author
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Zhi-Xing Cao, Shengyong Yang, Wei-Wei Li, Qi-Zheng Sun, Shao-Hua Yao, Jin-Feng Shang, Hui-Wen Yang, Xin Chen, and Chuan Cheng
- Subjects
0301 basic medicine ,Cancer Research ,Pathology ,medicine.medical_specialty ,Skin Neoplasms ,Melanoma, Experimental ,Down-Regulation ,Antineoplastic Agents ,Dermatology ,Melanocyte ,Small Molecule Libraries ,Melanin ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Melanoma ,Zebrafish ,Microphthalmia-Associated Transcription Factor ,biology ,business.industry ,Neural crest ,Cell migration ,medicine.disease ,Microphthalmia-associated transcription factor ,biology.organism_classification ,Embryonic stem cell ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,business - Abstract
Melanoma is a type of cancer arising from the melanocytes, which are the cells that make up the pigment melanin and are derived from the neural crest. There is no particularly effective therapy once the disease is metastatic, highlighting the need for discovery of novel potent agents. In this investigation, we adopted a zebrafish embryonic pigmentation model to identify antimelanoma agents by screening an in-house small molecule library. With this assay, we found that a small molecule compound, SKLB226, blocked zebrafish pigmentation and pigment cell migration. Mechanism of action studies showed that SKLB226 downregulated MITF mRNA level in both zebrafish embryos and mammalian melanoma cells. Further studies showed that it could efficiently suppress the viability and migration of mammalian melanoma cells. In summary, SKLB226 can be used as a chemical tool to study melanocyte development as well as an antimelanoma lead compound that should be subjected to further structural optimization.
- Published
- 2016