A sesquiterpene lactone from Siegesbeckia glabrescens suppresses Hedgehog/Gli‑mediated transcription in pancreatic cancer cells

  • Authors:
    • Hwa Jin Lee
    • Qian Wu
    • Hua Li
    • Gyu‑Un Bae
    • An Keun Kim
    • Jae‑Ha Ryu
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  • Published online on: August 10, 2016     https://doi.org/10.3892/ol.2016.4994
  • Pages: 2912-2917
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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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October-2016
Volume 12 Issue 4

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Lee HJ, Wu Q, Li H, Bae GU, Kim AK and Ryu JH: A sesquiterpene lactone from Siegesbeckia glabrescens suppresses Hedgehog/Gli‑mediated transcription in pancreatic cancer cells. Oncol Lett 12: 2912-2917, 2016
APA
Lee, H.J., Wu, Q., Li, H., Bae, G., Kim, A.K., & Ryu, J. (2016). A sesquiterpene lactone from Siegesbeckia glabrescens suppresses Hedgehog/Gli‑mediated transcription in pancreatic cancer cells. Oncology Letters, 12, 2912-2917. https://doi.org/10.3892/ol.2016.4994
MLA
Lee, H. J., Wu, Q., Li, H., Bae, G., Kim, A. K., Ryu, J."A sesquiterpene lactone from Siegesbeckia glabrescens suppresses Hedgehog/Gli‑mediated transcription in pancreatic cancer cells". Oncology Letters 12.4 (2016): 2912-2917.
Chicago
Lee, H. J., Wu, Q., Li, H., Bae, G., Kim, A. K., Ryu, J."A sesquiterpene lactone from Siegesbeckia glabrescens suppresses Hedgehog/Gli‑mediated transcription in pancreatic cancer cells". Oncology Letters 12, no. 4 (2016): 2912-2917. https://doi.org/10.3892/ol.2016.4994