The flavonoid apigenin potentiates the growth inhibitory effects of gemcitabine and abrogates gemcitabine resistance in human pancreatic cancer cells

Matthew J. Strouch, Benjamin M. Milam, Laleh G. Melstrom, John J. McGill, Mohammad R. Salabat, Michael B. Ujiki, Xian Zhong Ding, David J. Bentrem

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

OBJECTIVES: The aim of the study was to evaluate the effect of combination therapy of apigenin and gemcitabine on cell proliferation, the cell cycle, and gemcitabine resistance in human pancreatic cancer cells. METHODS: Cell counting was used to assess the effect of single-agent and combination treatment on the proliferation of CD18 and AsPC-1 pancreatic cancer cells. Flow cytometry was performed to assess the effect of combination treatment on cell cycle progression and induction of apoptosis. Western blot analysis was used to evaluate phosporylated AKT (pAkt) and cell cycle proteins. The effect of apigenin on gemcitabine-resistant AsPC-1 cells was assessed via thymidine incorporation. RESULTS: Apigenin in combination with gemcitabine inhibited pancreatic cancer cell proliferation more than either agent alone. Combination treatment induced both S and G2/M phase arrest and increased apoptosis. Apigenin down-regulated pAkt expression and abrogated gemcitabine-mediated pAkt induction. In gemcitabine-resistant AsPC-1 cells, apigenin significantly inhibited cell proliferation in a dose-dependent manner. CONCLUSION: Combination treatment with apigenin and gemcitabine inhibited pancreatic cancer cell growth via cell cycle arrest, down-regulation of the prosurvival factor pAkt, and induction of apoptosis. Combination therapy may prove useful for the treatment of pancreatic cancer.

Original languageEnglish (US)
Pages (from-to)409-415
Number of pages7
JournalPancreas
Volume38
Issue number4
DOIs
StatePublished - May 1 2009

Keywords

  • Apigenin
  • Cell cycle
  • Chemoresistance
  • Flavonoid
  • Gemcitabine
  • Pancreatic cancer

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Hepatology
  • Endocrinology

Fingerprint Dive into the research topics of 'The flavonoid apigenin potentiates the growth inhibitory effects of gemcitabine and abrogates gemcitabine resistance in human pancreatic cancer cells'. Together they form a unique fingerprint.

  • Cite this