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

doi:10.1038/s41598-020-77028-8

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

Weizmann Institute of Science

Research output: Contribution to journal › Article › peer-review

18 Scopus citations

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.

Original language	English
Article number	20030
Journal	Scientific Reports
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41598-020-77028-8
State	Published - 18 Nov 2020
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2020, The Author(s).

Funding

The study supported by a grant from the Nancy and Stephen Grand Israel National Center for Personalized Medicine. The SGC library was supplied by the Structural Genomics Consortium under an Open Science Trust Agreement: https://www.thesgc.org/click-trust . We would like to thank Nissan Industries (Japan) for providing us with SpheraMax synthetic polymer, Dr. Zeev Elazar lab for GFP-expressed HT-29 cells, the Department of Veterinary Resources for help with tumor tissue histology and immunohistochemistry.

Funders	Funder number
Nancy and Stephen Grand Israel National Center for Personalized Medicine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Plotnikov, A., Kozer, N., Cohen, G., Carvalho, S., Duberstein, S., Almog, O., Solmesky, L. J., Shurrush, K. A., Babaev, I., Benjamin, S., Gilad, S., Kupervaser, M., Levin, Y., Gershovits, M., Ben-Avraham, D., & Barr, H. M. (2020). PRMT1 inhibition induces differentiation of colon cancer cells. Scientific Reports, 10(1), Article 20030. https://doi.org/10.1038/s41598-020-77028-8

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PRMT1 inhibition induces differentiation of colon cancer cells

Abstract

Bibliographical note

Funding

UN SDGs

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