PRMT1 inhibition induces differentiation of colon cancer cells

ABSTRACT: Colorectal cancer (CRC) is the third most commonly occurring cancer in men and the second most commonly occurring cancer in women, with over 1.8 million new cases in 20181. Differentiation therapy has been recently revisited as a prospective approach in cancer therapy2 by targeting the aberrant growth, differentiation and cell death programs of cancer cells. Standard of care chemotherapy may eradicate cancer cells, but the aggressive cells can survive and resistance gradually develops. In contrast, differentiation therapy aims not to eradicate cancer bulk, but rather directs cancer cells towards inhibited proliferation and restoration of the apoptotic program, while maintaining a limited toxicity. Current data suggests that differentiation therapy can be an effective anti-cancer treatment approach, however discovery of the new differentiation inducing molecules with a higher therapeutic index is essential. We performed HTS screen for compounds mediating differentiation of colon cancer cell using a novel dual multiplex assay3. Here we show that PRMT type 1 inhibitor MS023 is a potent inducer of colon cancer cell differentiation with a large therapeutic window. Our findings has a great importance for following investigation and development of effective differentiation based anti CRC therapy applicable in the clinic.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Colon

SUBMITTER: Meital Kupervaser  

LAB HEAD: Barr Haim

PROVIDER: PXD016799 | Pride | 2021-09-09

REPOSITORIES: Pride