PRMT1 inhibition induces differentiation of colon cancer cells

Alexander Plotnikov, Noga Kozer, Galit Cohen, Silvia Carvalho, Shirly Duberstein, Ofir Almog, Leonardo Javier Solmesky, Khriesto A. Shurrush, Ilana Babaev, Sima Benjamin, Shlomit Gilad, Meital Kupervaser, Yishai Levin, Michael Gershovits, Danny Ben-Avraham, Haim Michael Barr

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14 Scopus citations


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.

Original languageEnglish
Article number20030
JournalScientific Reports
Issue number1
StatePublished - Dec 2020
Externally publishedYes

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