Diarylidenylpiperidones, H-4073 and HO-3867, Induce G2/M Cell-Cycle Arrest, Apoptosis and Inhibit STAT3 Phosphorylation in Human Pancreatic Cancer Cells

Jesse M. Mast, Dan Tse, Kevin Shee, M. Lakshmi Kuppusamy, Maciej M. Kmiec, T. Kalai, Periannan Kuppusamy

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Abstract

Pancreatic cancer has a 5-year survival rate below 10% and the treatment options are limited. Signal transducer and activator of transcription (STAT3) is a constitutively expressed protein in human pancreatic cancers and is associated with their poor prognosis. Targeting of STAT3 signaling using novel therapeutic agents is a potential strategy for pancreatic cancer treatment. Diarylidenylpiperidone (DAP) compounds, such as H-4073 and HO-3867, have been shown to be STAT3 inhibitors in several human ovarian cancers. Particularly, HO-3867 is an N-hydroxypyrroline derivative of DAP that has targeted cytotoxicity toward cancer cells without affecting healthy cells. In the present study, we evaluated the anticancer efficacy of H-4073 and HO-3867 in a human pancreatic cell line (AsPC-1). We found that both the compounds exhibited potential cytotoxicity to AsPC-1 cells by inducing G2/M cell-cycle arrest, apoptosis, and cell death, by mitochondrial damage and inhibition of STAT3 phosphorylation. In summary, H-4073 and HO-3867 are cytotoxic to AsPC-1 cells and seem to act through similar mechanisms, including STAT3 inhibition, cell-cycle arrest, and apoptosis.

Original languageEnglish
Pages (from-to)109-119
Number of pages11
JournalCell Biochemistry and Biophysics
Volume77
Issue number2
DOIs
Publication statusPublished - Jun 15 2019

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Keywords

  • Apoptosis
  • Diarylidenylpiperidone
  • Nitroxide
  • Pancreatic cancer
  • Reactive oxygen species
  • STAT3

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Cell Biology

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