Guggulsterone inhibits angiogenesis by blocking STAT3 and VEGF expression in colon cancer cells

Eun Soo Kim, Sung Yi Hong, Hye Kyung Lee, Seung Won Kim, Min Jin An, Tae Il Kim, Kyoung Ryul Lee, Won Ho Kim, Jea Hee Cheon

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

The plant sterol guggulsterone has been shown to exert anti-tumor effects, making it a candidate chemotherapeutic agent. We investigated the anti-tumor effects of guggulsterone on colon cancer cells and elucidated the underlying molecular mechanisms related to angiogenesis. The apoptotic effects of guggulsterone were examined by cell survival assay. Western blot analysis was used to determine the levels of various down-stream intracellular proteins involved in angiogenesis, including signal transducer and activator of transcription 3 (STAT3), vascular endothelial growth factor (VEGF), hypoxia-inducible factor-1α (HIF-1α) and aryl hydrocarbon receptor nuclear translocator (ARNT). Using chromatin immunoprecipitation assay, we tested whether guggulsterone affects the recruitment of STAT3, ARNT and HIF-1α to the human VEGF promoter. To investigate the effect of guggulsterone on vascular endothelial cell migration and invasion, tube formation and migration assays were conducted using human umbilical vein endothelial cells (HUVECs). Matrix metalloproteinase (MMP)-2 and -9 activities were measured by gelatin zymography. Guggulsterone significantly reduced cell viability in colon cancer cells in a dose-dependent manner and blocked VEGF, ARNT and STAT3 expression prominently in hypoxic conditions. The recruitment of STAT3 and ARNT, but not HIF-1α, to the VEGF promoter was inhibited by guggulsterone treatment. HUVECs produced much foreshortened and severely broken tubes and showed decreased migration activity under guggulsterone effects. In addition, zymography revealed that MMP-2 and -9 enzyme activities were markedly lower in the presence of guggulsterone. The results of this study suggest that guggulsterone not only induces apoptosis, but also inhibits angiogenesis and metastasis in colon cancer cells by blocking STAT3 and VEGF expression, suggesting its therapeutic potential in the treatment of colorectal cancer.

Original languageEnglish
Pages (from-to)1321-1327
Number of pages7
JournalOncology Reports
Volume20
Issue number6
DOIs
Publication statusPublished - 2008 Dec 1

Fingerprint

STAT3 Transcription Factor
Colonic Neoplasms
Vascular Endothelial Growth Factor A
Aryl Hydrocarbon Receptor Nuclear Translocator
Hypoxia-Inducible Factor 1
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
Human Umbilical Vein Endothelial Cells
Cell Survival
pregna-4,17-diene-3,16-dione
Phytosterols
Chromatin Immunoprecipitation
Gelatin
Cell Movement
Colorectal Neoplasms
Neoplasms
Endothelial Cells
Western Blotting
Apoptosis
Neoplasm Metastasis

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Kim, Eun Soo ; Hong, Sung Yi ; Lee, Hye Kyung ; Kim, Seung Won ; An, Min Jin ; Kim, Tae Il ; Lee, Kyoung Ryul ; Kim, Won Ho ; Cheon, Jea Hee. / Guggulsterone inhibits angiogenesis by blocking STAT3 and VEGF expression in colon cancer cells. In: Oncology Reports. 2008 ; Vol. 20, No. 6. pp. 1321-1327.
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Kim, ES, Hong, SY, Lee, HK, Kim, SW, An, MJ, Kim, TI, Lee, KR, Kim, WH & Cheon, JH 2008, 'Guggulsterone inhibits angiogenesis by blocking STAT3 and VEGF expression in colon cancer cells', Oncology Reports, vol. 20, no. 6, pp. 1321-1327. https://doi.org/10.3892/or_00000147

Guggulsterone inhibits angiogenesis by blocking STAT3 and VEGF expression in colon cancer cells. / Kim, Eun Soo; Hong, Sung Yi; Lee, Hye Kyung; Kim, Seung Won; An, Min Jin; Kim, Tae Il; Lee, Kyoung Ryul; Kim, Won Ho; Cheon, Jea Hee.

In: Oncology Reports, Vol. 20, No. 6, 01.12.2008, p. 1321-1327.

Research output: Contribution to journalArticle

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AU - Kim, Eun Soo

AU - Hong, Sung Yi

AU - Lee, Hye Kyung

AU - Kim, Seung Won

AU - An, Min Jin

AU - Kim, Tae Il

AU - Lee, Kyoung Ryul

AU - Kim, Won Ho

AU - Cheon, Jea Hee

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