The inhibition of angiogenesis and tumor growth by denbinobin is associated with the blocking of insulin-like growth factor-1 receptor signaling

An Chi Tsai, Shiow Lin Pan, Chin Yu Lai, Chih Ya Wang, Chien Chih Chen, Chien Chang Shen, Che Ming Teng

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Denbinobin, which is a phenanthraquinone derivative present in the stems of Ephemerantha lonchophylla, has been demonstrated to display antitumor activity. Recent reports suggest that the enhanced activity of insulin-like growth factor-1 receptor (IGF-1R) is closely associated with tumor angiogenesis and growth. This study aims at investigating the roles of denbinobin in suppressing these effects and at further elucidating the underlying molecular mechanisms. In the present study, we used an in vivo xenograft model antitumor and the Matrigel implant assays to show that denbinobin suppresses lung adenocarcinoma A549 growth and microvessel formation. Additionally, crystal violet and capillary-like tube formation assays indicated that denbinobin selectively inhibits insulin-like growth factor-1 (IGF-1)-induced proliferation (GI50=1.3×10-8 M) and tube formation of human umbilical vascular endothelial cells (HUVECs) without influencing the effect of epidermal growth factor; vascular endothelial growth factor and basic fibroblast growth factor. Furthermore, denbinobin inhibited the IGF-1-induced migration of HUVECs in a concentration-dependent fashion. Western blotting and immunoprecipitation demonstrated that denbinobin causes more efficient inhibition of IGF-1-induced activation of IGF-1R and its downstream signaling targets, including , extracellular signal-regulated kinase, Akt, mTOR, p70S6K, 4EBP and cyclin D1. All of our results provide evidences that denbinobin suppresses the activation of IGF-1R and its downstream signaling pathway, which leads to the inhibition of angiogenesis. Our findings suggest that denbinobin may be a novel IGF-1R kinase inhibitor and has potential therapeutic abilities for angiogenesis-related diseases such as cancer.

Original languageEnglish
Pages (from-to)625-633
Number of pages9
JournalJournal of Nutritional Biochemistry
Volume22
Issue number7
DOIs
Publication statusPublished - Jul 2011

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Somatomedin Receptors
Somatomedins
Tumors
Growth
Neoplasms
Umbilicus
Endothelial cells
Assays
Endothelial Cells
Chemical activation
70-kDa Ribosomal Protein S6 Kinases
Gentian Violet
denbinobin
Cyclin D1
Extracellular Signal-Regulated MAP Kinases
Fibroblast Growth Factor 2
Microvessels
Immunoprecipitation
Epidermal Growth Factor
Heterografts

Keywords

  • Angiogenesis
  • Denbinobin
  • Endothelial cell
  • Insulin-like growth factor-1 receptor
  • Lung adenocarcinoma A549

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

Cite this

The inhibition of angiogenesis and tumor growth by denbinobin is associated with the blocking of insulin-like growth factor-1 receptor signaling. / Tsai, An Chi; Pan, Shiow Lin; Lai, Chin Yu; Wang, Chih Ya; Chen, Chien Chih; Shen, Chien Chang; Teng, Che Ming.

In: Journal of Nutritional Biochemistry, Vol. 22, No. 7, 07.2011, p. 625-633.

Research output: Contribution to journalArticle

Tsai, An Chi ; Pan, Shiow Lin ; Lai, Chin Yu ; Wang, Chih Ya ; Chen, Chien Chih ; Shen, Chien Chang ; Teng, Che Ming. / The inhibition of angiogenesis and tumor growth by denbinobin is associated with the blocking of insulin-like growth factor-1 receptor signaling. In: Journal of Nutritional Biochemistry. 2011 ; Vol. 22, No. 7. pp. 625-633.
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AU - Chen, Chien Chih

AU - Shen, Chien Chang

AU - Teng, Che Ming

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