title: 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.affiliation: Department of Pharmacology & Therapeutics, United Arab Emirates University, Al-Ain, United Arab Emirates. samir.attoub@uaeu.ac.ae
authors.forename: Samir
authors.initials: S
authors.lastname: Attoub
authors.forename: Ahmed H
authors.initials: AH
authors.lastname: Hassan
authors.forename: Barbara
authors.initials: B
authors.lastname: Vanhoecke
authors.forename: Rabah
authors.initials: R
authors.lastname: Iratni
authors.forename: Takashi
authors.initials: T
authors.lastname: Takahashi
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Gaben
authors.forename: Marc
authors.initials: M
authors.lastname: Bracke
authors.forename: Salma
authors.initials: S
authors.lastname: Awad
authors.forename: Anne
authors.initials: A
authors.lastname: John
authors.forename: Hamda Ahmed
authors.initials: HA
authors.lastname: Kamalboor
authors.forename: Mahmood Ahmed
authors.initials: MA
authors.lastname: Al Sultan
authors.forename: Kholoud
authors.initials: K
authors.lastname: Arafat
authors.forename: Christian
authors.initials: C
authors.lastname: Gespach
authors.forename: Georg
authors.initials: G
authors.lastname: Petroianu
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D020170:Caspase 1 / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D004032:Diet; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D015622:Epithelioid Cells / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D005260:Female; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D047311:Luteolin / Q000494:pharmacology*; D051379:Mice; D009361:Neoplasm Invasiveness / Q000517:prevention & control; D009369:Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D056572:Histone Deacetylase Inhibitors; D006657:Histones; D053148:Caspase 3; D020170:Caspase 1; D006655:Histone Deacetylases; D047311:Luteolin; D002945:Cisplatin