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

• Published in: Archives of pharmacal research 2017, 40(4), , pp.509-517
• Main Authors: Dong, Guang-zhi, Jeong, Ji Hye, Lee, Yu-ih, Lee, So Yoon, Zhao, Hui-Yuan, Jeon, Raok, Lee, Hwa Jin, Ryu, Jae-Ha
• Format: Article
• Language: English
• Subjects: 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; Hedgehog Proteins - antagonists & inhibitors; Hedgehog Proteins - metabolism; HEK293 Cells; Humans; Medicine; Molecular Structure; Pharmacology/Toxicology; Pharmacy; Research Article; Structure-Activity Relationship; Zinc Finger Protein GLI1 - antagonists & inhibitors; Zinc Finger Protein GLI1 - metabolism; 약학
• ISSN: 0253-6269; 1976-3786
• DOI: 10.1007/s12272-017-0905-2

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.