Summary
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 µM) 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 µM) 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.
References
Jordan VC, Mittal S, Gosden B, Koch R, Lieberman ME: Structure-activity relationships of estrogens. Environ Health Perspec 61: 97–110, 1985
Berthois Y, Katzenellenbogen JA, Katzenellenbogen BS: Phenol red in tissue culture media is a weak estrogen: implications concerning the study of estrogen response of cells in culture. Proc Natl Acad Sci 83: 2496–2500, 1986
Vamossy Z: Ueber ein neues Abführpurgen. Therapie der Gegenwart 43: 201, 1902
Sharaiha ZK, Sackman JW, Graham DY: Comparison of phenolphthalein and phenolphthalein glucuronide on net water transport in rat ileum and colon. Digest Dis Sci 28: 827–832, 1983
Capasso F, Mascolo N, Autore G, Duraccio MR: Suppression of laxative action of phenolphthalein by orally-administered indomethacin or aspirin. J Pharm Pharmacol 36: 132–133, 1983
Fantus B, Dyniewicz JM: Phenolphthalein studies. A thousand doses of phenolphthalein: urinanalyses. JAMA 108: 439–443, 1937
Fantus B, Dyniewicz JM: Phenolphthalein studies. Elimination of phenolphthalein. JAMA 110: 796–799, 1938
Shafie SM, Brooks SC: Effects of prolactin on growth and estrogen receptor level of human breast cancer cells (MCF-7). Cancer Res 37: 792–797, 1977
Lowry OH, Rosenbrough NJ, Farr AL, Randall RJ: Protein determination with the Folin-phenol reagent. J Biol Chem 193: 265–275, 1951
Labarca C, Paigen K: A simple, rapid, and sensitive DNA assay procedure. Anal Biochem 102: 344–349, 1980
The Merck Index, tenth edition, page 1451–1452, 1983
Dodds EC, Lawson W: Synthetic oestrogenic agents without the phenanthrene nucleus. Nature 137: 996, 1936
Emmens CW: Halogen substituted oestrogens related to triphenylethylene. J Endocrinol 5: 170–173, 1947
Jordan VC: Biochemical pharmacology of antiestrogen action. Pharmacol Rev 36: 245–276, 1984
Colburn WA, Hiron PC, Parker RJ, Milburn P: A pharmacokinetic model for the enterohepatic recirculation in the rat: phenolphthalein, a model drug. Drug Metab Dispos 7: 100–102, 1979
Hirom PC, Milburn P, Parker RJ: The enterohepatic circulation of3H-phenolphthalein in the rat. Proc Brit Pharmacol Soc 355P, 1975
Visek WJ, Liu WC, Roth LJ: Studies on the fate of carbon-14 labeled phenolphthalein. J Pharmacol Exp Ther 116: 347–357, 1956
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Ravdin, P.M., van Beurden, M. & Jordan, V.C. Estrogenic effects of phenolphthalein on human breast cancer cellsin vitro . Breast Cancer Res Tr 9, 151–154 (1987). https://doi.org/10.1007/BF01807368
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DOI: https://doi.org/10.1007/BF01807368