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A sesquiterpene lactone from Siegesbeckia glabrescens suppresses Hedgehog/Gli-mediated transcription in pancreatic cancer cellsopen access

Authors
Lee, Hwa JinWu, QianLi, HuaBae, Gyu-UnKim, An KeunRyu, Jae-Ha
Issue Date
Oct-2016
Publisher
SPANDIDOS PUBL LTD
Keywords
Siegesbeckia glabrescens; compositae; sesquiterpene lactone; pancreatic cancer; Gli; Hedgehog pathway
Citation
ONCOLOGY LETTERS, v.12, no.4, pp 2912 - 2917
Pages
6
Journal Title
ONCOLOGY LETTERS
Volume
12
Number
4
Start Page
2912
End Page
2917
URI
https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/9412
DOI
10.3892/ol.2016.4994
ISSN
1792-1074
1792-1082
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 from Siegesbeckia glabrescens as 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 from S. glabrescens may therefore serve as a candidate for the treatment of Hh/Gli-dependent pancreatic cancer.
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