Apigenin down-regulates the hypoxia response genes: HIF-1α, GLUT-1, and VEGF in human pancreatic cancer cells

Laleh G. Melstrom, Mohammad R. Salabat, Xian Zhong Ding, Matthew J. Strouch, Paul J. Grippo, Salida Mirzoeva, Jill C. Pelling, David J. Bentrem

Research output: Contribution to journalArticle

56 Scopus citations

Abstract

Background: The flavonoid apigenin exhibits anti-proliferative and anti-angiogenic activities. Our objective was to evaluate the effect of apigenin on hypoxia responsive genes important in pancreatic cancer cell proliferation. Materials and Methods: Immunohistochemistry for GLUT-1 expression was conducted on human pancreatic cancer samples and adjacent controls. Real-time RT-PCR, Western blot analysis, and enzyme-linked immunosorbent assay (ELISA) were conducted on CD18 and S2-013 human pancreatic cancer cells treated with apigenin (0-50 μM) in normoxic and hypoxic conditions to evaluate HIF-1α, GLUT-1, and VEGF mRNA and protein expression and secretion. Results: GLUT-1 expression was significantly increased in pancreatic adenocarcinoma samples versus adjacent controls (P < 0.001). Hypoxic conditions induced HIF-1α, GLUT-1, and VEGF protein expression in both CD18 and S2-013 pancreatic cancer cells. Apigenin (50 μM) blocked hypoxia induced up-regulation of all three proteins in both cell lines. Apigenin also impeded hypoxia-mediated induction of GLUT-1 and VEGF mRNA in both cell lines (P < 0.05). Conclusions: Apigenin inhibits HIF-1α, GLUT-1, and VEGF mRNA and protein expression in pancreatic cancer cells in both normoxic and hypoxic conditions. This may account for the mechanism of apigenin's anti-proliferative and anti-angiogenic effects and further supports the potential of apigenin as a future chemopreventive agent for pancreatic cancer.

Original languageEnglish (US)
Pages (from-to)173-181
Number of pages9
JournalJournal of Surgical Research
Volume167
Issue number2
DOIs
StatePublished - May 15 2011

Keywords

  • GLUT-1
  • HIF-1α
  • VEGF
  • apigenin
  • hypoxia
  • pancreatic cancer

ASJC Scopus subject areas

  • Surgery

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