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: Contribution to journalArticle

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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G2 Phase Cell Cycle Checkpoints
Phosphorylation
Pancreatic Neoplasms
Cells
Apoptosis
Cytotoxicity
Cell Cycle Checkpoints
Transducers
Oncology
Ovarian Neoplasms
Cell death
Transcription
Cell Death
Cell Line
(3,5-bis((4-fluorophenyl)methylidene)-1-((1-hydroxy-2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrol-3-yl)methyl)piperidin-4-one)
Derivatives
Neoplasms
Proteins

Keywords

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

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Cell Biology

Cite this

Diarylidenylpiperidones, H-4073 and HO-3867, Induce G2/M Cell-Cycle Arrest, Apoptosis and Inhibit STAT3 Phosphorylation in Human Pancreatic Cancer Cells. / Mast, Jesse M.; Tse, Dan; Shee, Kevin; Lakshmi Kuppusamy, M.; Kmiec, Maciej M.; Kalai, T.; Kuppusamy, Periannan.

In: Cell Biochemistry and Biophysics, Vol. 77, No. 2, 15.06.2019, p. 109-119.

Research output: Contribution to journalArticle

Mast, Jesse M. ; Tse, Dan ; Shee, Kevin ; Lakshmi Kuppusamy, M. ; Kmiec, Maciej M. ; Kalai, T. ; Kuppusamy, Periannan. / Diarylidenylpiperidones, H-4073 and HO-3867, Induce G2/M Cell-Cycle Arrest, Apoptosis and Inhibit STAT3 Phosphorylation in Human Pancreatic Cancer Cells. In: Cell Biochemistry and Biophysics. 2019 ; Vol. 77, No. 2. pp. 109-119.
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