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KMID : 0043320170400040509
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Archives of Pharmacal Research
2017 Volume.40 No. 4 p.509 ~ p.517
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Diarylheptanoids suppress proliferation of pancreatic cancer PANC-1 cells through modulating shh-Gli-FoxM1 pathway
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Dong Guang Zhi
Jeong Ji-Hye
Lee Yu-Ih
Lee So-Yoon
Zhao Hui Yuan
Jeon Ra-Ok
Lee Hwa-Jin
Ryu Jae-Ha
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Abstract
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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.
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KEYWORD
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Diarylheptanoids, Alpinia officinarum, Alnus japonica, FoxM1, Gli, PANC-1 pancreatic cancer cell, (E)-7-(4-hydroxy-3-methoxyphenyl)-1-phenylhept-4-en-3-one, Platyphyllenone
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