Dual targeting of retinoid X receptor and histone deacetylase with DW22 as a novel antitumor approach

Oncotarget
Lihui WangChunfu Wu

Abstract

Retinoid X receptor (RXR) and Histone deacetylase (HDAC) are considered important targets for cancer therapy due to their crucial roles in genetic or epigenetic regulations of cancer development and progression. Here, we evaluated the potential of dual targeting of RXR and HDAC using DW22 as a novel therapeutic approach to cancer treatment. We found that the co-expression of RXR-α and HDAC1 was frequently appeared in lung cancer and breast cancer tissues and cell lines. RXR was activated by DW22 in RXRα and HDAC1 overexpressed A549 and MDA-MB-435 cell lines. Meanwhile, DW22 inhibited the activity of HDAC by decreasing its expression in A549 and MDA-MB-435 cell lines, but not in RXRα and HDAC1 deficient cell lines. Moreover, DW22 suppressed cell growth, induced cell differentiation, prompted cell apoptosis and arrested cell cycle in A549, MDA-MB-435 or HL60 cell lines. Treatment human umbilical vascular endothelial cells (HUVECs) with DW22 suppressed migration, invasion and tube formation through decreasing VEGF expression. The up-regulation of Ac-H3 and p21, and down-regulation of VEGF caused by DW22 was markedly attenuated by silencing of HDAC1. Furthermore, knockdown of RXRα by siRNA completely blocked DW22-induced cell diffe...Continue Reading

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Citations

Jun 21, 2019·Medicina·Alexandra Iulia IrimieIoana Berindan-Neagoe
Nov 5, 2020·European Journal of Medicinal Chemistry·Gargi Nikhil VaidyaDinesh Kumar

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Methods Mentioned

BETA
acetylation
PCR
ChIP
FACS
biosensor
xenograft
xenografts
fluorescence resonance
LanthaScreen
Assay

Software Mentioned

RTCA
ImageXpress
ImageXpress R
SPSS11

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