PRMT1 inhibition induces differentiation of colon cancer cells.

Scientific Reports
Alexander PlotnikovHaim Michael Barr

Abstract

Differentiation therapy has been recently revisited as a prospective approach in cancer therapy by targeting the aberrant growth, and repairing the differentiation and cell death programs of cancer cells. However, differentiation therapy of solid tumors is a challenging issue and progress in this field is limited. We performed High Throughput Screening (HTS) using a novel dual multiplex assay to discover compounds, which induce differentiation of human colon cancer cells. Here we show that the protein arginine methyl transferase (PRMT) type 1 inhibitor, MS023, is a potent inducer of colon cancer cell differentiation with a large therapeutic window. Differentiation changes in the highly aggressive human colon cancer cell line (HT-29) were proved by proteomic and genomic approaches. Growth of HT-29 xenograft in nude mice was significantly delayed upon MS023 treatment and immunohistochemistry of tumor indicated differentiation changes. These findings may lead to development of clinically effective anti-cancer drugs based on the mechanism of cancer cell differentiation.

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Citations

Jun 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Małgorzata MilczarekKatarzyna Wiktorska

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Datasets Mentioned

BETA
GSE142314
PXD016799

Methods Mentioned

BETA
transfection
thermal shift
xenograft
xenografts
PCR
acetylation

Software Mentioned

Ingenuity
GraphPad Prism
cutadapt
GeneData
Maxquant
Collaborative Drug Discover ( CDD )
MetaXpress
GraphPad
DESeq2
Metamorph scoring

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