title: Luteolin induces cell cycle arrest and apoptosis through extrinsic and intrinsic signaling pathways in MCF-7 breast cancer cells.
abstract: Luteolin is a common flavonoid that exists in medicinal herbs, fruits, and vegetables. Luteolin has biochemical functions including anti-allergy, anti-inflammation, and anti-cancer functions. However, its efficacy and precise mode of action against breast cancer are still under study. To elucidate whether luteolin exhibits an anticancer effect in breast cancer, MCF-7 breast cancer cells were incubated with luteolin, and apoptosis was assessed by observing nuclear morphological changes and by performing cell viability assay, cell cycle analysis, annexin V-FITC/PI double staining, western blotting, RT-PCR, and mitochondrial membrane potential measurements. Luteolin inhibited growth through perturbation of cell cycle progression at the sub-G1 and G1 phases in MCF-7 cells. Furthermore, luteolin enhanced the expression of death receptors, such as DR5, and activated caspase cascades. It enhanced the activities of caspase-8/-9/-3 in a dose-dependent manner, followed by inactivation of PARP. Activation of caspase-8 and caspase-9 induced caspase-3 activity, respectively, in apoptosis of extrinsic and intrinsic pathways. Luteolin also induced mitochondrial membrane potential collapse and cytochrome c release, and increased Bax expression by inhibiting expression of Bcl-2. Taken together, these results suggest that luteolin provokes cell cycle arrest and induces apoptosis by activating the extrinsic and intrinsic pathways.
authors.affiliation: Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University; 120, Neungdongro, Gwangjin-gu, Seoul 143-701, Republic of Korea.
authors.forename: Su-Ho
authors.initials: SH
authors.lastname: Park
authors.affiliation: Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University; 120, Neungdongro, Gwangjin-gu, Seoul 143-701, Republic of Korea.
authors.forename: Sunyoung
authors.initials: S
authors.lastname: Ham
authors.affiliation: Aging Research Center, Korea Research Institute of Bioscience & Biotechnology, 125, Gwahak-ro, Yuseong-gu, Daejeon 306-809, Republic of Korea.
authors.forename: Tae Ho
authors.initials: TH
authors.lastname: Kwon
authors.affiliation: Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University; 120, Neungdongro, Gwangjin-gu, Seoul 143-701, Republic of Korea.
authors.forename: Man Sub
authors.initials: MS
authors.lastname: Kim
authors.affiliation: Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University; 120, Neungdongro, Gwangjin-gu, Seoul 143-701, Republic of Korea.
authors.forename: Dong Hun
authors.initials: DH
authors.lastname: Lee
authors.affiliation: Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University; 120, Neungdongro, Gwangjin-gu, Seoul 143-701, Republic of Korea.
authors.forename: Jeoung-Woo
authors.initials: JW
authors.lastname: Kang
authors.affiliation: Natural Medicine Research Center, Bio-Therapeutics Research Institute, Korea Research Institute of Bioscience & Biotechnology, Ochang-eup, Cheongwon-gun, ChungBuk 363-883, Republic of Korea.
authors.forename: Sei-Ryang
authors.initials: SR
authors.lastname: Oh
authors.affiliation: Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University; 120, Neungdongro, Gwangjin-gu, Seoul 143-701, Republic of Korea.
authors.forename: Do-Young
authors.initials: DY
authors.lastname: Yoon
mesh_terms: D017302:Annexins / Q000737:chemistry; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D002467:Cell Nucleus / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D016650:Fluorescein-5-isothiocyanate / Q000737:chemistry; D006801:Humans; D047311:Luteolin / Q000494:pharmacology*; D061986:MCF-7 Cells; D053078:Membrane Potential, Mitochondrial; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D017302:Annexins; D000970:Antineoplastic Agents; D016650:Fluorescein-5-isothiocyanate; D047311:Luteolin