MITF suppression by CH5552074 inhibits cell growth in melanoma cells
| Autor: | Toshihiko Fujii, Munehiro Yuhki, Satoshi Aida, Takakazu Mizuno, Kiyoaki Sakata, Hiroshi Sakamoto, Yukiko Sonobe |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cancer Research Skin Neoplasms Antineoplastic Agents Biology Toxicology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell Line Tumor medicine Humans Pharmacology (medical) RNA Small Interfering Melanoma neoplasms Transcription factor Cell Proliferation Pharmacology Microphthalmia-Associated Transcription Factor Gene knockdown integumentary system Cell growth Imidazoles Microarray Analysis medicine.disease Microphthalmia-associated transcription factor Gene Expression Regulation Neoplastic Thiazoles 030104 developmental biology Oncology chemistry Cell culture Gene Knockdown Techniques 030220 oncology & carcinogenesis Immunology Cancer research Drug Screening Assays Antitumor Skin cancer Growth inhibition Cell Division |
| Zdroj: | Cancer Chemotherapy and Pharmacology. 79:1187-1193 |
| ISSN: | 1432-0843 0344-5704 |
| DOI: | 10.1007/s00280-017-3317-6 |
| Popis: | Although treatment of melanoma with BRAF inhibitors and immune checkpoint inhibitors achieves a high response rate, a subset of melanoma patients with intrinsic and acquired resistance are insensitive to these therapeutics, so to improve melanoma therapy other target molecules need to be found. Here, we screened our chemical library to identify an anti-melanoma agent and examined its action mechanisms to show cell growth inhibition activity. We screened a chemical library against multiple skin cancer cell lines and conducted ingenuity pathway analysis (IPA) to investigate the mechanisms of CH5552074 activity. Suppression of microphthalmia-associated transcription factor (MITF) expression levels was determined in melanoma cells treated with CH5552074. Cell growth inhibition activity of CH5552074 was evaluated in MITF-dependent melanoma cell lines. We identified an anti-melanoma compound, CH5552074, which showed remarkable cell growth inhibition activity in melanoma cell lines. The IPA results suggested that CH5552074-sensitive cell lines had activated MITF. In further in vitro studies in the melanoma cell lines, a knockdown of MITF with siRNA resulted in cell growth inhibition, which showed that CH5552074 inhibited cell growth by reducing the expression level of MITF protein. These results suggest that CH5552074 can inhibit cell growth in melanoma cells by reducing the protein level of MITF. MITF inhibition by CH5552074 would be an attractive option for melanoma treatment. |
| Databáze: | OpenAIRE |
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