Estrogen synthesis in human colon cancer epithelial cells.

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Fiorelli G, Picariello L, Martineti V, Tonelli F, Brandi ML

Estrogen synthesis in human colon cancer epithelial cells.

J Steroid Biochem Mol Biol. 1999 Dec 31;71(5-6):223-30.

PubMed ID

10704911 [ View in PubMed

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Abstract

Epidemiological and experimental data suggest an involvement of estrogen in the development and progression of colorectal cancer. In order to determine whether local synthesis of estrogen occurred in human colonic cancer cells, two colorectal cancer cell lines, HCT8 and HCT116, were evaluated for gene expression and enzyme activity of cytochrome P450 aromatase. In addition, the effect on aromatase expression of charcoal-stripped fetal calf serum, of quercetin and genistein and of tamoxifen and raloxifene was investigated in both cell lines. RT-PCR analysis revealed that colorectal adenocarcinoma cell lines contain aromatase as a major component. The conversion of [(3)H]-androstenedione to estrone and labeled water was dose-dependently inhibited by 4-hydroxyandrostenedione and obeyed Michaelis-Menten kinetic with apparent Km values of approximately 20 nM and V(max) values of approx. 200 and 500 fmol/mg protein/h for HCT8 and HCT116 cells, respectively. After 24 h incubation, genistein (1 microM) significantly increased aromatase activity in HCT8 cells, with no effect on HCT116 cells. In accord with previous observation in reproductive tissues, quercetin (1 microM) significantly inhibited the enzyme activity in both cell lines. Also tamoxifen (100 nM) acted as inhibitor, while raloxifene (10 nM) decreased the enzyme activity only in HCT116 cells. The aromatase gene expression modulation by these effective agents was consistent with their effects on enzyme activity. These findings demonstrate for the first time that colorectal adenocarcinoma cell lines express aromatase. Interestingly, the enzyme activity was inhibited by quercetin, one major dietary flavonoid, by tamoxifen, a hormonal therapeutic agent for breast cancer, and by raloxifene, used in the prevention of postmenopausal osteoporosis.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Raloxifene	Cytochrome P450 19A1	Protein	Humans	Unknown	Inhibitor	Details
Tamoxifen	Cytochrome P450 19A1	Protein	Humans	Unknown	Inhibitor	Details

Pharmaco-transcriptomics

Drug	Drug Groups	Gene	Gene ID	Change	Interaction	Chromosome
Quercetin	Experimental Investigational	CYP19A1	1588	downregulated	Quercetin results in decreased expression of CYP19A1 mRNA	15q21.2
Raloxifene	Approved Investigational	CYP19A1	1588	downregulated	Raloxifene Hydrochloride results in decreased expression of CYP19A1 mRNA	15q21.2
Tamoxifen	Approved	CYP19A1	1588	downregulated	Tamoxifen results in decreased expression of CYP19A1 mRNA	15q21.2