title: Extra virgin olive oil potentiates the effects of aromatase inhibitors via glutathione depletion in estrogen receptor-positive human breast cancer (MCF-7) cells.
abstract: There have been numerous evidences supporting the relationship between olive oil and cancer, with most of the attention being directed toward its fat and phenolic content. The aims of this study were to investigate whether EVOO and OA could enhance the effects of aromatase inhibitors (letrozole and anastrozole) in ER-positive MCF-7 cells, as well as to investigate its influence on cytochrome c release and GSH levels. It was observed that upon combination treatment, anti-proliferation effects and apoptosis induction were augmented. Apoptosis was triggered via the intrinsic pathway in accordance with cytochrome c release into the cytosol based on IF-IC and ELISA observations. Intracellular GSH levels were also reduced upon EVOO/OA treatment in combination with aromatase inhibitors, and were found to be inversely correlated to cytosolic cytochrome c levels. Additionally, the estrogenic suppressive effects of letrozole and anastrozole were amplified when used in combination with EVOO/OA. Therefore, the employment of aromatase inhibitors in combination with EVOO/OA could orchestrate a reduction in intracellular estrone biosynthesis which feeds ER-positive cells, while simultaneously depleting GSH levels and increasing ROS generation, thus releasing cytochrome c and subsequent induction of apoptosis in MCF-7 cells.
authors.affiliation: Department of Pathology, Faculty of Medicine and Health Sciences, Al-Neelain University, 12702 Khartoum, Sudan; Department of Biochemistry, Faculty of Science and Technology, Al-Neelain University, 12702 Khartoum, Sudan. Electronic address: amarqqqu@yahoo.com.
authors.forename: Amar Mohamed
authors.initials: AM
authors.lastname: Ismail
authors.forename: Lionel L A
authors.initials: LL
authors.lastname: In
authors.forename: Mohammad
authors.initials: M
authors.lastname: Tasyriq
authors.forename: Devi Rosmy
authors.initials: DR
authors.lastname: Syamsir
authors.forename: Khalijah
authors.initials: K
authors.lastname: Awang
authors.forename: Ayda Hussein Omer
authors.initials: AH
authors.lastname: Mustafa
authors.forename: Omer Fadul
authors.initials: OF
authors.lastname: Idris
authors.forename: Imad
authors.initials: I
authors.lastname: Fadl-Elmula
authors.forename: Noor
authors.initials: N
authors.lastname: Hasima
mesh_terms: D000077384:Anastrozole; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D047072:Aromatase Inhibitors / Q000494:pharmacology*; D045304:Cytochromes c / Q000378:metabolism; D005260:Female; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D000077289:Letrozole; D061986:MCF-7 Cells / Q000187:drug effects; D009570:Nitriles / Q000494:pharmacology; D019301:Oleic Acid / Q000494:pharmacology; D000069463:Olive Oil; D010938:Plant Oils / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D014230:Triazoles / Q000494:pharmacology
chemical_list: D047072:Aromatase Inhibitors; D009570:Nitriles; D000069463:Olive Oil; D010938:Plant Oils; D017382:Reactive Oxygen Species; D011960:Receptors, Estrogen; D014230:Triazoles; D019301:Oleic Acid; D000077384:Anastrozole; D000077289:Letrozole; D045304:Cytochromes c; D005978:Glutathione
keywords: Apoptosis; Aromatase inhibitor; B-Cell Lymphoma 2; Bcl-2; Breast cancer; E1; ER; EVOO; Estrogen; FA; GSH; MUFA; NADPH; Nicotinamide Adenine Dinucleotide Phosphate; OA; OO; Oleic acid; Olive oil; PUFA; estrogen receptor; estrone; extra virgin olive oil; fatty acids; glutathione; monounsaturated fatty acid; oleic acid; olive oil; polyunsaturated fatty acid