Combination Effects of Hispidin and Gemcitabine via Inhibition of Stemness in Pancreatic Cancer Stem Cells

Anticancer Res. 2018 Jul;38(7):3967-3975. doi: 10.21873/anticanres.12683.


Background/aim: Natural products extracted from plants can be potent for developing pharmaceutical products. Hispidin, a polyphenolic compound mainly derived from the medicinal mushroom Phellinus linteus, has been shown to have a therapeutic potential against cancer cells. Pancreatic cancer is one of the most aggressive solid malignancies with high resistance to existing drugs. Cancer stem cells (CSCs) are responsible for chemoresistance. The present study aimed to evaluate the anticancer effects of hispidin on pancreatic CSCs.

Materials and methods: The cytotoxic effects of hispidin on BxPC-3 and AsPC-1 pancreatic cancer cells and BxPC-3 CD44+ CSCs and the synergistic effects of gemcitabine and hispidin on CSCs were evaluated by a series of in vitro experiments including the 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), fluorescence-activated cell sorting, colony forming, Transwell assay, immunocytochemistry, sphere-forming, and western blot assays.

Results: Hispidin exerted antitumor effects against both BxPC-3 pancreatic cancer cells and CSCs. Furthermore, it was found that hispidin sensitized pancreatic CSCs to gemcitabine and promoted the therapeutic efficacy of gemcitabine.

Conclusion: Hispidin might be a novel chemosensitizer for gemcitabine and a potential synergistic agent for increasing the therapeutic index of gemcitabine as a treatment for pancreatic cancer.

Keywords: Hispidin; NF-κB; cancer stem cells; gemcitabine; pancreatic cancer.

MeSH terms

  • Blotting, Western
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives*
  • Deoxycytidine / pharmacology
  • Down-Regulation / drug effects
  • Drug Resistance, Neoplasm
  • Humans
  • Neoplastic Stem Cells / drug effects*
  • Pancreatic Neoplasms / pathology*
  • Pyrones / administration & dosage
  • Pyrones / pharmacology*


  • Pyrones
  • Deoxycytidine
  • gemcitabine
  • hispidin