Synthesis and biological evaluation of a novel anticancer agent CBISC that induces DNA damage response and diminishes levels of mutant-p53.

Biochem Biophys Res Commun

Integrated Biosciences Graduate Program, University of Minnesota, Duluth, MN, 55812, USA; Department of Pharmacy Practice & Pharmaceutical Sciences, University of Minnesota, Duluth, MN, 55812, USA; Department of Chemistry and Biochemistry, University of Minnesota Duluth, Duluth, MN, 55812, USA. Elec

Published: July 2021


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Article Abstract

A novel nitrogen mustard CBISC has been synthesized and evaluated as an anticancer agent. CBISC has been shown to exhibit enhanced cell proliferation inhibition properties against mutant p53 cell lines colorectal cancer WiDr, pancreatic cancer (MIAPaCa-2 and PANC-1), and triple negative breast cancer (MDA-MB-231 and MDA-MB-468). In vitro mechanism of action studies revealed perturbations in the p53 pathway and increased cell death as evidenced by western blotting, immunofluorescent microscopy and MTT assay. Further, in vivo studies revealed that CBISC is well tolerated in healthy mice and exhibited significant in vivo tumor growth inhibition properties in WiDr and MIAPaCa-2 xenograft models. These studies illustrate the potential utility of CBISC as an anticancer agent.

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http://dx.doi.org/10.1016/j.bbrc.2021.05.062DOI Listing

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