(3E,5E)-3,5-Bis(pyridin-3-methylene)-tetrahydrothiopyran-4-one enhances the inhibitory effect of gemcitabine on pancreatic cancer cells

Panpan Wu, Xiao Wang, Yuran Ma, Xuetao Xu, Wenfeng Liu, Zhaojun Sheng, Min Chen, Renping Zhou, Kun Zhang, Susan Goodin, Xi Zheng, Dongli Li

Research output: Contribution to journalArticle

Abstract

Gemcitabine (GEM) is a commonly used treatment for advanced pancreatic cancer. However, chemoresistance and toxic side effect limits its clinical success. In an earlier study, our laboratory found that the curcumin analogue, (3E,5E)-3,5-Bis(pyridin-3-methylene)-tetrahydrothiopyran-4-one (FN2) had strong inhibitory effect on human pancreatic cancer cells. In the present study, we investigated the effects of FN2 in combination with GEM on growth inhibition and apoptosis in human pancreatic cancer Panc-1 cells. The results showed that the combination of FN2 and GEM synergistically inhibited the growth of Panc-1 cells. Panc-1 cells survived the GEM treatment became partially resistant to the drug. Treatment with FN2 in combination with GEM strongly inhibited the growth and stimulated apoptosis in the GEM resistant Panc-1 cells. Mechanistic studies showed that inhibition of cell growth and induction of apoptosis in the GEM resistant Panc-1 cells were associated with decreases in activation of NF-κB and Akt. FN2 in combination with GEM also decreased the level of Bcl-2 and increased the level of Bax. Results of the present study indicate that GEM in combination with FN2 may represent an effective strategy for improving the efficacy of GEM and decreasing the resistance of pancreatic cancer to GEM chemotherapy.

Original languageEnglish (US)
Article number104022
JournalBioorganic Chemistry
Volume101
DOIs
StatePublished - Aug 2020

All Science Journal Classification (ASJC) codes

  • Drug Discovery
  • Molecular Biology
  • Biochemistry
  • Organic Chemistry

Keywords

  • Apoptosis
  • Curcumin analogue
  • Gemcitabine
  • NF-κB
  • Pancreatic cancer

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