Inhibition of cell survival, invasion, tumor growth and histone deacetylase activity by the dietary flavonoid luteolin in human epithelioid cancer cells

Eur J Pharmacol. 2011 Jan 25;651(1-3):18-25. doi: 10.1016/j.ejphar.2010.10.063. Epub 2010 Nov 11.


Phytochemical compounds and histone deacetylase (HDAC) inhibitors are emerging as a new generation of anticancer agents with limited toxicity in cancer patients. We investigated the impact of luteolin, a dietary flavonoid, on survival, migration, invasion of cancer cells in vitro, and tumor growth in vivo. Luteolin (25-200μM) decreased the viability of human cancer cell lines originating from the lung (LNM35), colon (HT29), liver (HepG2) and breast (MCF7/6 and MDA-MB231-1833). Luteolin effectively increased the sub-G1 (apoptotic) fraction of cells through caspase-3 and -7 dependent pathways. We provide evidence that luteolin at sub-lethal/non-toxic concentrations inhibited the invasive potential of LNM35, MCF-7/6 and MDA-MB231-1833 cancer cells using Matrigel as well as the chick heart and Oris invasion assays. Moreover, we demonstrate for the first time that luteolin is a potent HDAC inhibitor that potentiates the cytotoxicity of cisplatin in LNM35 cells and decreases the growth of LNM35 tumor xenografts in athymic mice after intraperitoneal injection (20mg/kg/day for 18days) Thus, luteolin, in combination with standard anticancer drugs such as cisplatin, may be a promising HDAC inhibitor for the treatment of lung cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation / drug effects
  • Animals
  • Apoptosis / drug effects
  • Caspase 1 / metabolism
  • Caspase 3 / metabolism
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cisplatin / pharmacology
  • Diet*
  • Drug Synergism
  • Enzyme Activation / drug effects
  • Epithelioid Cells / drug effects*
  • Epithelioid Cells / enzymology
  • Epithelioid Cells / metabolism
  • Epithelioid Cells / pathology*
  • Female
  • Histone Deacetylase Inhibitors / pharmacology*
  • Histone Deacetylases / metabolism*
  • Histones / metabolism
  • Humans
  • Luteolin / pharmacology*
  • Mice
  • Neoplasm Invasiveness / prevention & control
  • Neoplasms / enzymology
  • Neoplasms / metabolism
  • Neoplasms / pathology*
  • Xenograft Model Antitumor Assays


  • Histone Deacetylase Inhibitors
  • Histones
  • Caspase 3
  • Caspase 1
  • Histone Deacetylases
  • Luteolin
  • Cisplatin