International Journal of Molecular Sciences | |
Phenotypic Identification of the Redox Dye Methylene Blue as an Antagonist of Heat Shock Response Gene Expression in Metastatic Melanoma Cells | |
Angela L. Davis1  Christopher M. Cabello1  Shuxi Qiao1  Sara Azimian1  | |
[1] Pharmacology and Toxicology, College of Pharmacy, Arizona Cancer Center, University of Arizona, Tucson, AZ 85724, USA; | |
关键词: malignant melanoma; heat shock response; Hsp70; Hsp27; methylene blue; chemosensitization; | |
DOI : 10.3390/ijms14024185 | |
来源: mdpi | |
【 摘 要 】
Repurposing approved and abandoned non-oncological drugs is an alternative developmental strategy for the identification of anticancer therapeutics that has recently attracted considerable attention. Due to the essential role of the cellular heat shock response in cytoprotection through the maintenance of proteostasis and suppression of apoptosis, small molecule heat shock response antagonists can be harnessed for targeted induction of cytotoxic effects in cancer cells. Guided by gene expression array analysis and a phenotypic screen interrogating a collection of 3,7-diamino-phenothiazinium derivatives, we have identified the redox-drug methylene blue (MB), used clinically for the infusional treatment of methemoglobinemia, as a negative modulator of heat shock response gene expression in human metastatic melanoma cells. MB-treatment blocked thermal (43 °C) and pharmacological (celastrol, geldanamycin) induction of heat shock response gene expression, suppressing Hsp70 (
【 授权许可】
CC BY
© 2013 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland.
【 预 览 】
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