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

Abstract

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.

• Authors: Samir Attoub, Ahmed H Hassan, Barbara Vanhoecke, Rabah Iratni, Takashi Takahashi, Anne-Marie Gaben, Marc Bracke, Salma Awad, Anne John, Hamda Ahmed Kamalboor, Mahmood Ahmed Al Sultan, Kholoud Arafat, Christian Gespach, Georg Petroianu
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 651 Issue 1-3 Pg. 18-25 (Jan 25 2011) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 21074525 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2010 Elsevier B.V. All rights reserved.

Chemical References

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

Topics

• 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, enzymology, metabolism, pathology)
• Female
• Histone Deacetylase Inhibitors (pharmacology)
• Histone Deacetylases (metabolism)
• Histones (metabolism)
• Humans
• Luteolin (pharmacology)
• Mice
• Neoplasm Invasiveness (prevention & control)
• Neoplasms (enzymology, metabolism, pathology)
• Xenograft Model Antitumor Assays