title: A sesquiterpene lactone fromSiegesbeckia glabrescenssuppresses Hedgehog/Gli-mediated transcription in pancreatic cancer cells.
abstract: Pancreatic cancer is aggressive and therefore difficult to treat; however, continued efforts have been made with the aim of developing an effective therapy against the disease. The Hedgehog (Hh) signaling pathway is reportedly involved in the proliferation and survival of pancreatic cancer cells. The transcription factor glioma-associated oncogene (Gli) is a key component of the Hh signaling pathway and the primary effector of pancreatic cancer development. Inhibiting Gli is a proven therapeutic strategy for this disease. The present study examined the regulation of Gli and the expression of its target genes to identify an inhibitor of the Sonic Hh (Shh) pathway. A germacranolide sesquiterpene lactone (GSL) was isolated fromSiegesbeckia glabrescensas an inhibitor of Gli-mediated transcription. The results demonstrated that GSL inhibited Shh-induced osteoblast differentiation and Gli homolog 1 (Gli1)-mediated transcriptional activity in mesenchymal C3H10T1/2 stem cells. Furthermore, GSL suppressed Gli-mediated transcriptional activity in human pancreatic cancer PANC-1 and AsPC-1 cells, which resulted in reduced cancer cell proliferation and downregulated expression of the Gli-target genes, Gli1 and cyclin D1. A sesquiterpene lactone fromS. glabrescensmay therefore serve as a candidate for the treatment of Hh/Gli-dependent pancreatic cancer.
authors.affiliation: Department of Natural Medicine Resources, Semyung University, Jecheon, Chungcheongbuk-do 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, Seoul 140-742, Republic of Korea.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Research Center for Cell Fate Control and College of Pharmacy, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.affiliation: Research Center for Cell Fate Control and College of Pharmacy, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
authors.forename: Gyu-Un
authors.initials: GU
authors.lastname: Bae
authors.affiliation: Research Center for Cell Fate Control and College of Pharmacy, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
authors.forename: An Keun
authors.initials: AK
authors.lastname: Kim
authors.affiliation: Research Center for Cell Fate Control and College of Pharmacy, Sookmyung Women's University, Seoul 140-742, Republic of Korea.
authors.forename: Jae-Ha
authors.initials: JH
authors.lastname: Ryu
keywords: Gli; Hedgehog pathway; Siegesbeckia glabrescens; compositae; pancreatic cancer; sesquiterpene lactone