Diarylheptanoids suppress proliferation of pancreatic cancer PANC-1 cells through modulating shh-Gli-FoxM1 pathway

Arch Pharm Res. 2017 Apr;40(4):509-517. doi: 10.1007/s12272-017-0905-2. Epub 2017 Mar 3.


Pancreatic cancer is one of the leading causes of cancer, and it has the lowest 5-year survival rates. It is necessary to develop more potent anti-pancreatic cancer drugs to overcome the fast metastasis and resistance to surgery, radiotherapy, chemotherapy, and combinations of these. We have identified several diarylheptanoids as anti-pancreatic cancer agents from Alpinia officinarum (lesser galangal) and Alnus japonica. These diarylheptanoids suppressed cell proliferation and induced the cell cycle arrest of pancreatic cancer cells (PANC-1). Among them, the most potent compounds 1 and 7 inhibited the shh-Gli-FoxM1 pathway and their target gene expression in PANC-1 cells. Furthermore, they suppressed the expression of the cell cycle associated genes that were rescued by the overexpression of exogenous FoxM1. Taken together, (E)-7-(4-hydroxy-3-methoxyphenyl)-1-phenylhept-4-en-3-one (1) from Alpinia officinarum (lesser galangal) and platyphyllenone (7) from Alnus japonica inhibit PANC-1 cell proliferation by suppressing the shh-Gli-FoxM1 pathway, and they can be potential candidates for anti-pancreatic cancer drug development.

Keywords: (E)-7-(4-hydroxy-3-methoxyphenyl)-1-phenylhept-4-en-3-one; Alnus japonica; Alpinia officinarum; Diarylheptanoids; FoxM1; Gli; PANC-1 pancreatic cancer cell; Platyphyllenone.

MeSH terms

  • Alpinia / chemistry*
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / isolation & purification
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Diarylheptanoids / chemistry
  • Diarylheptanoids / isolation & purification
  • Diarylheptanoids / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Forkhead Box Protein M1 / antagonists & inhibitors*
  • Forkhead Box Protein M1 / metabolism
  • HEK293 Cells
  • Hedgehog Proteins / antagonists & inhibitors*
  • Hedgehog Proteins / metabolism
  • Humans
  • Molecular Structure
  • Structure-Activity Relationship
  • Zinc Finger Protein GLI1 / antagonists & inhibitors*
  • Zinc Finger Protein GLI1 / metabolism


  • Antineoplastic Agents, Phytogenic
  • Diarylheptanoids
  • FOXM1 protein, human
  • Forkhead Box Protein M1
  • GLI1 protein, human
  • Hedgehog Proteins
  • SHH protein, human
  • Zinc Finger Protein GLI1