n-desmethyltamoxifen and Leukemia

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.

Topics: Binding Sites; Collagen; Estrogen Antagonists; Fibrinolysin; Humans; Leukemia; Plasminogen Inactivators; Tamoxifen; Tumor Cells, Cultured