Metabolic profiles of androgens in malignant human liver cell lines.
In this study we have investigated androgen (testosterone and androstenedione) metabolism in malignant HepG2, Huh-7, and HA22T human liver cell lines. Following 72-h incubation with testosterone or androstenedione, estrogen formation through aromatase activity was consistently higher in HepG2 cells (being nearly 100%) and moderate in Huh7 cells (34%), while it was undetectable in HA22T cells. The produced estrogens are completely conjugated by estrogen sulpho-transferase (EST) in HepG2 cells, while nearly 25% remains in the free form in Huh-7 cells. The HA22T and Huh-7 cells show a markedly different balance of 5alpha- versus 5beta-reduced androgens (65.7% vs. 2.5% and 2.6% vs. 22.2%, respectively), while no detectable 5alpha/5beta-reduced androgen is formed in HepG2 cells. These divergent metabolic profiles, coupling aromatase to EST, and to 5alpha/5beta-reductase, hint at a differential regulation of androgen metabolic pathways that may ultimately lead to a distinct impact of biologically active metabolites on growth and function of human liver cancer cells.
Granata
Orazia M
OM
Experimental Oncology Unit, Department of Oncology, P.O. M. Ascoli, ARNAS-Civico, Piazzale N. Leotta 2, 90127 Palermo, Italy.
Cocciadiferro
Letizia
L
Miceli
Vitale
V
Polito
Lucia M
LM
Campisi
Ildegarda
I
Carruba
Giuseppe
G
D000728:Androgens / Q000378:metabolism; D000735:Androstenedione / Q000378:metabolism* / Q000494:pharmacology; D001141:Aromatase / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004967:Estrogens / Q000032:analysis / Q000096:biosynthesis*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D015238:Sulfotransferases / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism* / Q000494:pharmacology
D000728:Androgens; D004967:Estrogens; D013739:Testosterone; D000735:Androstenedione; D001141:Aromatase; D015238:Sulfotransferases; C084556:ethinylestradiol-17 alpha sulfotransferase