title: Modulating potential of L-sulforaphane in the expression of cytochrome p450 to identify potential targets for breast cancer chemoprevention and therapy using breast cell lines.
abstract: The L-sulforaphane (SFN) component of broccoli sprout showed anticancer activity in several preclinical studies including breast cancer. Estrogens are considered major risk factors in breast carcinogenesis. The aim of this study was to evaluate the effect of SFN on the expression of cytochrome P450 involved in the estrogen metabolism in breast cancer cell lines MCF7 and MDA-MB-231 and in non-tumorigenic MCF10A cell line. The expression of CYP19, CYP1A1, 1A2, 1B1 was determined at the transcript and protein levels. There were found some remarkable differences in the effect of SFN at a dose of 5 µmol/L on CYP19 expression: in ER(+) MCF7 significant reduction, in ER(-) MDA-MB-231 an increased expression and unchanged expression in MCF10A cell line. The effect of SFN on CYPs (1A1, 1A2, 1B1) involved in estrogen catabolism was to a lesser extent dependent on breast cell line. The slightly reduced CYP1A1 protein level was observed in all cell lines tested. An increased level of CYP1A2 and decreased level of CYP1B1 expression were found in MCF10A. These results indicate that the naturally occurring L isomer of SFN may affect the expression of P450s involved in estrogen metabolism. This effect may contribute to the anticancer activity of SFN in breast tissue.
authors.affiliation: Department of Pharmaceutical Biochemistry, Poznan University of Medical Sciences, Poznań, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Licznerska
authors.forename: Hanna
authors.initials: H
authors.lastname: Szaefer
authors.forename: Iwona
authors.initials: I
authors.lastname: Matuszak
authors.forename: Marek
authors.initials: M
authors.lastname: Murias
authors.forename: Wanda
authors.initials: W
authors.lastname: Baer-Dubowska
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis; D001141:Aromatase / Q000378:metabolism; D001943:Breast Neoplasms / Q000201:enzymology; D045744:Cell Line, Tumor / Q000187:drug effects; D002470:Cell Survival; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D065633:Cytochrome P-450 CYP1B1 / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D006801:Humans; D017879:Isothiocyanates / Q000494:pharmacology*; D061986:MCF-7 Cells; D013454:Sulfoxides
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004967:Estrogens; D017879:Isothiocyanates; D013454:Sulfoxides; D003577:Cytochrome P-450 Enzyme System; D001141:Aromatase; C561410:CYP19A1 protein, human; C569463:CYP1A1 protein, human; C504573:CYP1A2 protein, human; C585496:CYP1B1 protein, human; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; D065633:Cytochrome P-450 CYP1B1; C016766:sulforaphane
keywords: CYP19; CYP1A1; CYP1A2; CYP1B1; L-Sulforaphane; breast cancer chemoprevention