Estrogenic effects of phenolphthalein on human breast cancer cells in vitro.
There is a structural similarity between phenolphthalein and the triphenylethylenes which are known to interact with the estrogen receptor of human breast tissue. Phenolphthalein (10 microM) competed with estrogen for binding to MCF-7 human breast cancer cells in tissue culture and induced the synthesis of the progesterone receptor. The antiestrogen 4-hydroxytamoxifen blocked progesterone receptor induction both by estradiol and by phenolphthalein. Both estradiol (0.1 nM) and phenolphthalein (10 microM) stimulated cell growth as measured by DNA and protein assays. This growth stimulation was blocked by 4-hydroxytamoxifen. Phenolphthalein glucuronide, the major phenolphthalein metabolite, did not inhibit estrogen binding, induce progesterone receptor synthesis, or stimulate MCF-7 cell growth in culture. Yellow phenolphthalein, an impure phenolphthalein preparation used in nonprescription laxative preparations, had similar properties to pure phenolphthalein. Physicians should be aware of the weak estrogenic action of phenolphthalein, especially when recommending laxatives for breast cancer patients with confirmed liver and mesenteric metastases.
D001667:Binding, Competitive; D001943:Breast Neoplasms / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D045166:Estradiol Congeners; D005965:Glucuronates; D006801:Humans; D020113:Phenolphthalein; D010635:Phenolphthaleins / Q000378:metabolism / Q000494:pharmacology*; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D013329:Structure-Activity Relationship
D045166:Estradiol Congeners; D005965:Glucuronates; D010635:Phenolphthaleins; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D020113:Phenolphthalein; D004247:DNA