title: Inhibition of collagenolytic activity in human leukemic K562 cells by tamoxifen.
abstract: Presence of a collagenolytic activity has been demonstrated in the human leukemic cell line K562. Among various effectors studied, tamoxifen, a well-known antiestrogenic compound, exhibited a strong inhibitory effect. After 3 days of culture in the presence of 10(-7) M of tamoxifen, 75% of the collagenolytic activity was inhibited. Hydroxytamoxifen and N-desmethyltamoxifen were equally potent inhibitors though devoid of the direct cytotoxic effect. Cis-tamoxifen was less efficient. K562 cells have no binding sites for estrogens but they possess high affinity binding sites for 3H-tamoxifen (295 fmol/mg of proteins, KD = 0.25 x 10(-9) M). Tamoxifen had no effect on cellular differentiation or enzyme secretion. Anticollagenolytic activity of tamoxifen (10(-7)-10(-6) M) could be related to its inhibitory action on plasmin and plasminogen activator.
authors.affiliation: G.I.B.S.A.-Groupe d'Etude des Interactions Biologiques de Substances Anticancéreuses, Laboratoire de Biochimie, Faculté de Pharmacie, Reims, France.
authors.forename: M G
authors.initials: MG
authors.lastname: Akeli
authors.forename: C
authors.initials: C
authors.lastname: Madoulet
authors.forename: A
authors.initials: A
authors.lastname: Rallet
authors.forename: J C
authors.initials: JC
authors.lastname: Jardillier
mesh_terms: D001665:Binding Sites; D003094:Collagen / Q000378:metabolism*; D004965:Estrogen Antagonists / Q000494:pharmacology; D005341:Fibrinolysin / Q000037:antagonists & inhibitors; D006801:Humans; D007938:Leukemia / Q000378:metabolism* / Q000473:pathology; D015849:Plasminogen Inactivators / Q000494:pharmacology; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
chemical_list: D004965:Estrogen Antagonists; D015849:Plasminogen Inactivators; D013629:Tamoxifen; C016601:afimoxifene; D003094:Collagen; D005341:Fibrinolysin; C028787:N-desmethyltamoxifen