ALTERATION IN PROLIFERATIVE AND ENDOCRINE RESPONSIVENESS OF HUMAN MAMMARY-CARCINOMA CELLS BY PROTOTYPIC TUMOR-SUPPRESSING AGENTS

The experiments performed in this study were designed to establish tha t (1) anchorage-independent independent growth, a biological character istic tumorigenically transformed phenotype, can be modulated by proto typic tumor-suppressing agents, and (2) modulation of growth is influe nced by the metabolic competence of the cells to biotransform estradio l. MCF-7 human breast carcinoma cells exhibited linear cell proliferat ive kinetics with a 41-hour population doubling time, and a 15% colony -forming efficiency in 0.33% agar. Indole-3-carbinol (I3C), a naturall y occurring tumor-suppressive agent; tamoxifen (TAM), an antiestrogeni c agent; and 4-hydroxytamoxifen (4-OHTAM), a metabolite of TAM, demons trated 73.7%, 72.5%, and 89.9% suppression in anchorage-independent gr owth of MCF-7 cells, respectively. At the metabolic level, I3C and 4-O HTAM induced 2.3-fold (P < 0.0001) and 1.3-fold increase (P = 0.001) r elative to their own controls in the extent of 2-hydroxylation of estr adiol. The results indicate that growth inhibition by I3C, TAM, and 4- OHTAM may in part be due to altered estradiol metabolism in MCF-7 cell s. This, anchorage-independent growth and altered biotransformation of estradiol may constitute useful cellular and endocrine markers to eva luate the biological response of chemosuppressiue agents.