title: Diarylheptanoids suppress proliferation of pancreatic cancer PANC-1 cells through modulating shh-Gli-FoxM1 pathway.
abstract: 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.
authors.affiliation: Research Center for Cell Fate Control and College of Pharmacy, Sookmyung Women's University, 52 Hyochanwon-Gil, Yongsan-Gu, Seoul, 140-742, Republic of Korea.
authors.forename: Guang-Zhi
authors.initials: GZ
authors.lastname: Dong
authors.affiliation: Research Center for Cell Fate Control and College of Pharmacy, Sookmyung Women's University, 52 Hyochanwon-Gil, Yongsan-Gu, Seoul, 140-742, Republic of Korea.
authors.forename: Ji Hye
authors.initials: JH
authors.lastname: Jeong
authors.affiliation: Research Center for Cell Fate Control and College of Pharmacy, Sookmyung Women's University, 52 Hyochanwon-Gil, Yongsan-Gu, Seoul, 140-742, Republic of Korea.
authors.forename: Yu-Ih
authors.initials: YI
authors.lastname: Lee
authors.affiliation: Research Center for Cell Fate Control and College of Pharmacy, Sookmyung Women's University, 52 Hyochanwon-Gil, Yongsan-Gu, Seoul, 140-742, Republic of Korea.
authors.forename: So Yoon
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Research Center for Cell Fate Control and College of Pharmacy, Sookmyung Women's University, 52 Hyochanwon-Gil, Yongsan-Gu, Seoul, 140-742, Republic of Korea.
authors.forename: Hui-Yuan
authors.initials: HY
authors.lastname: Zhao
authors.affiliation: Research Center for Cell Fate Control and College of Pharmacy, Sookmyung Women's University, 52 Hyochanwon-Gil, Yongsan-Gu, Seoul, 140-742, Republic of Korea.
authors.forename: Raok
authors.initials: R
authors.lastname: Jeon
authors.affiliation: Department of Natural Medicine Resources, Semyung University, 65 Semyung-Ro, Jecheon, Chungbuk, 390-711, Republic of Korea.
authors.forename: Hwa Jin
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Research Center for Cell Fate Control and College of Pharmacy, Sookmyung Women's University, 52 Hyochanwon-Gil, Yongsan-Gu, Seoul, 140-742, Republic of Korea. ryuha@sookmyung.ac.kr.
authors.forename: Jae-Ha
authors.initials: JH
authors.lastname: Ryu
mesh_terms: D032429:Alpinia / Q000737:chemistry*; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D036381:Diarylheptanoids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D000072278:Forkhead Box Protein M1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D057809:HEK293 Cells; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D000071676:Zinc Finger Protein GLI1 / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D036381:Diarylheptanoids; C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; C400551:GLI1 protein, human; D053823:Hedgehog Proteins; C509239:SHH protein, human; D000071676:Zinc Finger Protein GLI1
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