Novel microtubule inhibitor MPT0B098 inhibits hypoxia-induced epithelial-to-mesenchymal transition in head and neck squamous cell carcinoma

• Published in: Journal of biomedical science 2018-03, Vol.25 (1), p.28-28, Article 28
• Main Authors: Tsai, I-Ting, Kuo, Ching-Chuan, Liou, Jing-Ping, Chang, Jang-Yang
• Format: Article
• Language: English
• Subjects: Carcinoma, Squamous Cell - physiopathology; Cell Line, Tumor; Epithelial to mesenchymal transition; Epithelial-Mesenchymal Transition - drug effects; Head and neck cancer; Head and Neck Neoplasms - physiopathology; Humans; Hypoxia; Hypoxia - physiopathology; Hypoxia-Inducible Factor 1, alpha Subunit - antagonists & inhibitors; Indoles - pharmacology; Microtubule inhibitor; Squamous Cell Carcinoma of Head and Neck; Sulfonamides - pharmacology; TGF-β; Tubulin Modulators - pharmacology
• ISSN: 1423-0127; 1021-7770; 1423-0127
• DOI: 10.1186/s12929-018-0432-6

Tumor hypoxia-induced epithelial-mesenchymal transition (EMT) is critical in promoting cancer metastasis. We recently discovered a novel microtubule inhibitor, MPT0B098, that employs a novel antitumor mechanism. It destabilizes hypoxia-inducible factor (HIF)-1α mRNA by blocking the function of human antigen R. Thus, we proposed that MPT0B098 modulates hypoxia-induced EMT. In vitro IC values were determined through the methylene blue dye assay. To investigate molecular events, reverse transcriptase-polymerase chain reaction, Western blotting, immunofluorescence staining, and wound healing assay were employed. MPT0B098 significantly inhibited HIF-1α expression, epithelial-to-mesenchymal morphology changes, and migratory ability in the human head and neck squamous cell carcinoma cell line OEC-M1. Furthermore, after MPT0B098 treatment, the expression of two mesenchymal markers, vimentin and N-cadherin, was downregulated under hypoxic conditions. Moreover, MPT0B098 suppressed hypoxia-induced EMT in part by inhibiting EMT-activating transcription factors, Twist and SNAI2/Slug. In addition, the inhibition of hypoxia-induced F-actin rearrangement and focal adhesion kinase phosphorylation may have contributed to suppression of EMT by MPT0B098in OEC-M1 cells. MPT0B098 significantly inhibited transforming growth factor(TGF)-β-induced phosphorylation of receptor-associated Smad2/3 by downregulating TGF-β mRNA and protein expression. Taken together, this study provides a novel insight into the role of MPT0B098 in inhibiting hypoxia-induced EMT, suggesting its potential use for treating head and neck cancers.