Capsaicin regulates vascular endothelial cell growth factor expression by modulation of hypoxia inducing factor-1α in human malignant melanoma cells

Prabhudas S. Patel, Shillin Yang, Aihua Li, Michelle L. Varney, Rakesh K Singh

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Purpose: Capsaicin (8-Methyl-N-Vanillyl-6-nonenamide), a known natural dietary chemopreventive agent, inhibits malignant melanoma cell proliferation. In the present study, we examined the effect of capsaicin on constitutive and induced vascular endothelial cell growth factor (VEGF) expression in malignant melanoma cells. Results: Capsaicin treatment resulted in enhanced VEGF protein secretion in malignant melanoma cells independent of IL-1β and TNF-α. The observed up-regulation of VEGF production by capsaicin was concentration- and duration-dependent and was inversely associated with inhibition of melanoma cell proliferation. We observed an increase in hypoxia-inducible factor (HIF)-1α and VEGF mRNA expression in capsaicin-treated melanoma cells. Further, an electrophoretic mobility shift assay (EMSA) from nuclear extracts from melanoma cells showed a decrease in constitutive activation of NF-κB and enhanced HIF-1α binding activity to hypoxia response element (HRE) in melanoma cells treated with different concentrations of capsaicin. Conclusions: These data suggest that inhibition of cellular proliferation by capsaicin follows enhanced VEGF production by remaining melanoma cells by enhancing HIF-1α expression and binding to HRE.

Original languageEnglish (US)
Pages (from-to)461-468
Number of pages8
JournalJournal of Cancer Research and Clinical Oncology
Volume128
Issue number9
DOIs
StatePublished - Oct 9 2002

Fingerprint

Capsaicin
Vascular Endothelial Growth Factor A
Melanoma
Hypoxia-Inducible Factor 1
Cell Proliferation
Response Elements
Cell Hypoxia
Hypoxia
Electrophoretic Mobility Shift Assay
Cell Extracts
Interleukin-1
Up-Regulation
Messenger RNA

Keywords

  • Capsaicin
  • Malignant melanoma
  • VEGF

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Capsaicin regulates vascular endothelial cell growth factor expression by modulation of hypoxia inducing factor-1α in human malignant melanoma cells. / Patel, Prabhudas S.; Yang, Shillin; Li, Aihua; Varney, Michelle L.; Singh, Rakesh K.

In: Journal of Cancer Research and Clinical Oncology, Vol. 128, No. 9, 09.10.2002, p. 461-468.

Research output: Contribution to journalArticle

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