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Journal of Environmental Pathology, Toxicology and Oncology
IF: 1.625 5-Year IF: 1.63 SJR: 0.402 SNIP: 0.613 CiteScore™: 2.3

ISSN Print: 0731-8898
ISSN Online: 2162-6537

Journal of Environmental Pathology, Toxicology and Oncology

DOI: 10.1615/JEnvironPatholToxicolOncol.2014010923
pages 219-231

Luteolin Induces Cell Cycle Arrest and Apoptosis Through Extrinsic and Intrinsic Signaling Pathways in MCF-7 Breast Cancer Cells

Su-Ho Park
Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University; 120, Neungdongro, Gwangjin-gu, Seoul 143-701, Republic of Korea
Sunyoung Ham
Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University; 120, Neungdongro, Gwangjin-gu, Seoul 143-701, Republic of Korea
Tae Ho Kwon
Aging Research Center, Korea Research Institute of Bioscience & Biotechnology, 125, Gwahak-ro, Yuseong-gu, Daejeon 306-809, Republic of Korea
Man Sub Kim
Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University; 120, Neungdongro, Gwangjin-gu, Seoul 143-701, Republic of Korea
Dong Hun Lee
Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University; 120, Neungdongro, Gwangjin-gu, Seoul 143-701, Republic of Korea
Jeoung-Woo Kang
Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University; 120, Neungdongro, Gwangjin-gu, Seoul 143-701, Republic of Korea
Sei-Ryang Oh
Natural Medicine Research Center, Bio-Therapeutics Research Institute, Korea Research Institute of Bioscience & Biotechnology, Ochang-eup, Cheongwon-gun, ChungBuk 363-883, Republic of Korea
Do-Young Yoon
Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University; 120, Neungdongro, Gwangjin-gu, Seoul 143-701, Republic of Korea

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.


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