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

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

14 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 - Dec 2020
Externally published	Yes

Bibliographical note

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

UN SDGs

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

Access to Document

10.1038/s41598-020-77028-8

Cite this

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

@article{d4651a7492be418d816e39c915d3ada2,

title = "PRMT1 inhibition induces differentiation of colon cancer cells",

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.",

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

note = "Publisher Copyright: {\textcopyright} 2020, The Author(s).",

year = "2020",

month = dec,

doi = "10.1038/s41598-020-77028-8",

language = "אנגלית",

volume = "10",

journal = "Scientific Reports",

issn = "2045-2322",

publisher = "Nature Publishing Group",

number = "1",

}

TY - JOUR

T1 - PRMT1 inhibition induces differentiation of colon cancer cells

AU - Plotnikov, Alexander

AU - Kozer, Noga

AU - Cohen, Galit

AU - Carvalho, Silvia

AU - Duberstein, Shirly

AU - Almog, Ofir

AU - Solmesky, Leonardo Javier

AU - Shurrush, Khriesto A.

AU - Babaev, Ilana

AU - Benjamin, Sima

AU - Gilad, Shlomit

AU - Kupervaser, Meital

AU - Levin, Yishai

AU - Gershovits, Michael

AU - Ben-Avraham, Danny

AU - Barr, Haim Michael

PY - 2020/12

Y1 - 2020/12

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85096238521&partnerID=8YFLogxK

U2 - 10.1038/s41598-020-77028-8

DO - 10.1038/s41598-020-77028-8

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 33208761

AN - SCOPUS:85096238521

SN - 2045-2322

VL - 10

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 20030

ER -

PRMT1 inhibition induces differentiation of colon cancer cells

Abstract

Bibliographical note

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this