PRMT1 inhibition induces differentiation of colon cancer cells.


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
18 11 2020
Historique:
received: 14 05 2020
accepted: 04 11 2020
entrez: 19 11 2020
pubmed: 20 11 2020
medline: 2 4 2021
Statut: epublish

Résumé

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.

Identifiants

pubmed: 33208761
doi: 10.1038/s41598-020-77028-8
pii: 10.1038/s41598-020-77028-8
pmc: PMC7676271
doi:

Substances chimiques

Antineoplastic Agents 0
Biomarkers, Tumor 0
Repressor Proteins 0
PRMT1 protein, human EC 2.1.1.319
Protein-Arginine N-Methyltransferases EC 2.1.1.319

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

20030

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Auteurs

Alexander Plotnikov (A)

Wohl Institute for Drug Discovery, High Throughput Screening Unit, Grand Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot, Israel. alexander.plotnikov@weizmann.ac.il.

Noga Kozer (N)

Wohl Institute for Drug Discovery, High Throughput Screening Unit, Grand Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot, Israel.

Galit Cohen (G)

Wohl Institute for Drug Discovery, High Throughput Screening Unit, Grand Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot, Israel.

Silvia Carvalho (S)

Wohl Institute for Drug Discovery, High Throughput Screening Unit, Grand Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot, Israel.

Shirly Duberstein (S)

Wohl Institute for Drug Discovery, High Throughput Screening Unit, Grand Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot, Israel.

Ofir Almog (O)

Wohl Institute for Drug Discovery, High Throughput Screening Unit, Grand Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot, Israel.

Leonardo Javier Solmesky (LJ)

Wohl Institute for Drug Discovery, High Throughput Screening Unit, Grand Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot, Israel.

Khriesto A Shurrush (KA)

Wohl Institute for Drug Discovery, Medicinal Chemistry Unit, Grand Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot, Israel.

Ilana Babaev (I)

Wohl Institute for Drug Discovery, Medicinal Chemistry Unit, Grand Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot, Israel.

Sima Benjamin (S)

Crown Institute for Genomics, Grand Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot, Israel.

Shlomit Gilad (S)

Crown Institute for Genomics, Grand Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot, Israel.

Meital Kupervaser (M)

de Botton Institute for Proteomics, Grand Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot, Israel.

Yishai Levin (Y)

de Botton Institute for Proteomics, Grand Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot, Israel.

Michael Gershovits (M)

Mantoux Institute for Bioinformatics, Grand Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot, Israel.

Danny Ben-Avraham (D)

Mantoux Institute for Bioinformatics, Grand Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot, Israel.

Haim Michael Barr (HM)

Wohl Institute for Drug Discovery, High Throughput Screening Unit, Grand Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot, Israel.

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Classifications MeSH