Comparison of the effects of nobiletin and letrozole on the activity and expression of aromatase in the MCF-7 breast cancer cell line.
Nobiletin (NOB) is one of the polymethoxyflavones mainly found in citrus fruits. Aromatase or cytochrome P450 (CYP19) enzyme catalyzes the last and rate-limiting step in estrogen biosynthesis. This study was carried out to investigate the effect of NOB on the activity and expression of aromatase, and to compare this property with letrozole (LET) as aromatase inhibitor in the MCF-7 breast cancer cell line. Cell viability was assessed with 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assays. Aromatase enzyme activity based on the conversion of androgenic substrate testosterone into 17β-estradiol was determined. CYP19 gene expression was measured by quantitative real-time PCR. MTT assays demonstrated that NOB at a concentration of 100 μmol/L decreased cell viability in a time-dependent manner (P < 0.05). NOB significantly inhibited aromatase at the concentration of 0.1 μmol/L (P = 0.013), whereas other concentrations had no effect. Treatment with 10 μmol/L and 1 μmol/L of NOB for 48 h significantly increased (P = 0.001) and decreased (P = 0.02) relative aromatase expression, respectively. The combination of LET and NOB had no effect on aromatase. This study showed for the first time that NOB decreases the activity and expression of aromatase at low concentrations in MCF-7 breast cancer cells.
a Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran.
Seyedeh Tayebeh
ST
Rahideh
b Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Mohammad
M
Keramatipour
c Department of Biochemistry, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Mitra
M
Nourbakhsh
d Department of Molecular and Cellular Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.
Fariba
F
Koohdani
e Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
Mostafa
M
Hoseini
f Department of Genetics, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Saeed
S
Talebi
a Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran.
Farzad
F
Shidfar
D001141:Aromatase / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D047309:Flavones / Q000008:administration & dosage / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D000077289:Letrozole; D061986:MCF-7 Cells; D009570:Nitriles / Q000008:administration & dosage / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000008:administration & dosage / Q000494:pharmacology*
D047309:Flavones; D009570:Nitriles; D014230:Triazoles; D000077289:Letrozole; C008661:nobiletin; D001141:Aromatase
aromatase; breast cancer; cancer du sein; expression génique; gene expression; letrozole; létrozole; nobiletin; nobilétine