Action on Growth of Human Breast Cancer Cells ZR-75-1 and Interaction of Phenol Red with Estrogenic and Antiestrogenic

Studies reported here confirm that the pH indicator, phenol red, acts as a weak estrogen and reexamine the significance of estrogenic and antiestrogenic effects on growth of the human breast cancer cell lines ZR-75-1 and T-47-D in the absence of phenol red. Removal of phenol red reduces but does not immediately eliminate cell growth in the absence of estradici. Basal cell growth can be reduced for T-47-D cells and eliminated for ZR-75-1 cells by prior growth in the absence of steroid and phenol red for 3 weeks, demonstrating that estrogens can have long lasting effects on cells in culture (termed "steroid memory") and that there exist both cells which are responsive (T-47-D) and dependent (ZR75-1) on i-stradini for growth. Antiestrogen action in these cell lines is affected by at least four parameters: (a) presence of phenol red; (/>)time in culture; (c) cell density; (</) steroid memory effects. At high cell density, antiestrogens suppress phenol red-stimulated activity but have little effect in the absence of phenol red. However, at low cell density in the absence of phenol red, tamoxifen has a biphasic action: initial weak stimulation, later inhibition. rraà ̄u-Hydroxytarnoxifen does not stimulate but inhibition increases with time in culture. Following deprivation for 3 weeks of phenol red and steroid, antiestrogen action on ZR-75-1 cells at low density became much more inhibitory. Such responses to antiestro gens are discussed in relation to possible autocrine/paracrine growth regulation of the cells. Clinical relevance is suggested.