title: Luteolin attenuates doxorubicin-induced cytotoxicity to MCF-7 human breast cancer cells.
abstract: Luteolin, a flavone found in some vegetables, has been reported to exhibit antioxidant, antiinflammatory, and anticancer activities. In the present study, we found that luteolin has biphasic effects on the viability of the human breast cancer cell line MCF-7. That is, cell viability increased at relatively low luteolin concentrations and decreased at relatively high concentrations. Focusing on the proliferative effect at low concentrations, we showed that luteolin has a cytoprotective effect on MCF-7 cells when administered with doxorubicin. Moreover, luteolin attenuated doxorubicin-induced cytotoxicity even in the presence of the estrogen receptor (ER) antagonist ICI 182,780 and the ER-negative MDA-MB-453 human breast cancer cell line. Reactive oxygen species (ROS) were generated after doxorubicin treatment of MCF-7 cells. In contrast, luteolin attenuated doxorubicin-induced ROS generation. Levels of the antiapoptotic protein Bcl-2 in luteolin-treated MCF-7 cells were significantly higher than those in doxorubicin-treated MCF-7 cells. Our results suggest that a low concentration of luteolin attenuates doxorubicin-induced cytotoxicity to MCF-7 cells through a combination of antioxidant activity and an increase in levels of Bcl-2 protein.
authors.affiliation: Department of Health Chemistry, School of Pharmaceutical Sciences, Ohu University.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Sato
authors.forename: Naoto
authors.initials: N
authors.lastname: Sasaki
authors.forename: Megu
authors.initials: M
authors.lastname: Saito
authors.forename: Nao
authors.initials: N
authors.lastname: Endo
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Kugawa
authors.forename: Akemichi
authors.initials: A
authors.lastname: Ueno
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000975:Antioxidants / Q000009:adverse effects / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D018565:Food-Drug Interactions; D006801:Humans; D047311:Luteolin / Q000009:adverse effects* / Q000494:pharmacology; D061986:MCF-7 Cells; D010936:Plant Extracts / Q000009:adverse effects* / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D014675:Vegetables / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D051017:Apoptosis Regulatory Proteins; C000595707:BCL2 protein, human; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D011960:Receptors, Estrogen; D004317:Doxorubicin; D047311:Luteolin