title: A hydroxylated flavonol, fisetin inhibits the formation of a carcinogenic estrogen metabolite.
abstract: Fisetin can be found in a wide variety of plants and possesses strong efficacy against many cancers. 17β-Estradiol (E2) is hydrolyzed to 4-hydroxy-E2 (4-OHE2) via cytochrome P450 (CYP) 1B1 in vivo. In estrogen target tissues including the mammary gland, ovaries, and uterus, CYP1B1 is highly expressed, and 4-OHE2 is predominantly formed in cancerous tissues. Herein, we investigated the inhibitory activity of fisetin and flavone against CYP1B1 using estrogen E2 as substrate in vitro to reveal structure-activity relationship between structure of flavonoids and inhibition. The results showed that fisetin possessed inhibitory effect on CYP1B1 activity. Compared with flavone, the inhibition of fisetin was stronger. The Vmaxand Kivalues were 1.950±0.157pmol/μgprotein/min and 4.925±0.689nM for fisetin and 2.277±0.231pmol/μgprotein/min and 9.148±2.150nM for flavone, respectively. By kinetic analyses, both fisetin and flavone displayed mixed inhibition. Taken together the data suggested that fisetin is able to inhibit the formation of carcinogenic 4-OHE2 from E2, which reveals one of its anti-cancer mechanisms and helps to reveal the relationship between the structure of flavonoids and the inhibition CYP1B1 for discovering new drugs in cancer therapy and prevention.
authors.affiliation: School of Pharmacy, Heilongjiang University of Chinese Medicine, No. 24 Heping Road, Harbin 150040, PR China. Electronic address: mengxin52309@163.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Meng
authors.affiliation: School of Pharmacy, Heilongjiang University of Chinese Medicine, No. 24 Heping Road, Harbin 150040, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Sun
authors.affiliation: School of Pharmacy, Heilongjiang University of Chinese Medicine, No. 24 Heping Road, Harbin 150040, PR China.
authors.forename: Lianrong
authors.initials: L
authors.lastname: Yang
authors.affiliation: School of Pharmacy, Heilongjiang University of Chinese Medicine, No. 24 Heping Road, Harbin 150040, PR China.
authors.forename: Rui
authors.initials: R
authors.lastname: Yin
authors.affiliation: School of Pharmacy, Heilongjiang University of Chinese Medicine, No. 24 Heping Road, Harbin 150040, PR China.
authors.forename: Lehui
authors.initials: L
authors.lastname: Qi
mesh_terms: D002851:Chromatography, High Pressure Liquid; D004958:Estradiol / Q000378:metabolism; D004967:Estrogens / Q000737:chemistry / Q000378:metabolism; D005419:Flavonoids / Q000737:chemistry / Q000378:metabolism*; D044948:Flavonols / Q000737:chemistry / Q000378:metabolism*; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D004967:Estrogens; D005419:Flavonoids; D044948:Flavonols; D004958:Estradiol; C017875:fisetin
keywords: 17β-Estradiol (PubChem CID: 5757); Anti-tumor; Estradiol; Fisetin; Fisetin (PubChem CID: 5281614); Flavone (PubChem CID: 10680); Hormones