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Diarylheptanoids suppress proliferation of pancreatic cancer PANC-1 cells through modulating shh-Gli-FoxM1 pathway
- Dong, Guang-zhi, Jeong, Ji Hye, Lee, Yu-ih, Lee, So Yoon, Zhao, Hui-Yuan, Jeon, Raok, Lee, Hwa Jin, Ryu, Jae-Ha
- Archives of pharmacal research 2017 v.40 no.4 pp. 509-517
- Alnus japonica, Alpinia officinarum, cell cycle checkpoints, cell proliferation, drug therapy, drugs, gene overexpression, genes, metastasis, neoplasm cells, pancreatic neoplasms, radiotherapy, surgery, survival rate
- 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.