A Mercaptoacetamide-Based Class II Histone Deacetylase Inhibitor Suppresses Cell Migration and Invasion in Monomorphic Malignant Human Glioma Cells by Inhibiting FAK/STAT3 Signaling

Journal of Cellular Biochemistry
Jin Han NamHyang-Sook Hoe

Abstract

Histone deacetylase inhibitors (HDACIs) have emerged as potential anticancer agents for the treatment of solid and hematopoietic cancers. Several HDACIs delay cell growth, induce differentiation, or activate apoptosis in multiple types of tumors, including glioblastomas. In the present study, we showed that the mercaptoacetamide-based HDACI W2 inhibits cell migration and invasion in monomorphic malignant human glioma cells. W2 treatment significantly decreased the activity and expression levels of matrix metalloprotease-2 in malignant A172 cells but not in U373MG cells. Key signaling pathways involved in cell migration and invasion, including PI3K-AKT, ERK-JNK-P38, and FAK/STAT3, were examined to identify the mechanism of action of W2. W2 increased the phosphorylation of AKT and altered cell migration and invasion in an AKT-independent manner. W2 inhibited the phosphorylation of FAK/STAT3, and treatment with a FAK/STAT3 inhibitor significantly suppressed cancer cell migration and MMP-2 activity in the presence of W2. In addition, W2 significantly inhibited the nuclear translocation of phospho-STAT3. Taken together, our results suggest that W2 suppresses cancer cell migration and invasion by inhibiting FAK/STAT3 signaling and ST...Continue Reading

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Citations

Feb 15, 2018·BMC Cancer·Ewa TotonMaria Rybczynska
Sep 21, 2018·Journal of Neuroinflammation·Hye Yeon NamHyang-Sook Hoe
Jun 21, 2020·International Journal of Molecular Sciences·Jihyun ParkKwan-Kyu Park
Jul 20, 2020·Journal of Experimental & Clinical Cancer Research : CR·Rui ChenYali Wang
Mar 2, 2019·In Vitro Cellular & Developmental Biology. Animal·Banglian DengJun Chen
Oct 10, 2020·European Journal of Medicinal Chemistry·Maurício T TavaresSida Shen

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