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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.