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

Conor T. Ronayne, Sravan K. Jonnalagadda, Shirisha Jonnalagadda, Grady L. Nelson, Lucas N. Solano, Hithardha Palle, Chinnadurai Mani, Jon Rumbley, Jon Holy, Venkatram R. Mereddy

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)127-132
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume562
DOIs
StatePublished - Jul 12 2021

Bibliographical note

Funding Information:
This work was supported by University of Minnesota Duluth ; Whiteside Clinical Research Institute, Minnesota , and Randy Shaver Cancer Research and Community Fund, Minnesota .

Publisher Copyright:
© 2021

Keywords

  • Alkylating agent
  • Apoptosis
  • DNA-damage
  • MIAPaCa-2
  • Mutant p53
  • WiDr

PubMed: MeSH publication types

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

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