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

Research output: Article

2 Citations (Scopus)

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 - jún. 15 2019

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Cell Biology

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