In vitro synergism between estrogens and cytotoxic agents.
Two lines of research intending to achieve synergism between cytotoxic agents and estrogens for breast cancer treatment are pursued in our laboratory. According to a screening procedure we select cytotoxic-linked estrogens which bind to estrogen receptors and thereby would be specifically concentrated into the tumor cells. A mesylate derivative of estrone has emerged from our investigations. This compound displays a very strong binding affinity for the receptors and inhibits the growth of the receptor-positive MCF-7 breast cancer cell line. The lack of growth inhibition in the receptor-negative line Evsa-T indicates that it is devoid of major non-specific cytotoxicity. We attempt to enhance the vulnerability of the tumor cells by producing an estrogen-induced modification of their chromatin. The in vitro exposure of isolated uterine nuclei to uterine cytosol preincubated with estradiol increases their ability to bind [3H]actinomycin D. Identical results are obtained with MXT mouse mammary tumors. Experiments are in progress to settle whether these changes are associated with enhanced cell killing.
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002843:Chromatin / Q000187:drug effects; D003609:Dactinomycin / Q000627:therapeutic use; D003630:Daunorubicin / Q000627:therapeutic use; D004357:Drug Synergism; D004967:Estrogens / Q000627:therapeutic use*; D004970:Estrone / Q000627:therapeutic use; D006801:Humans; D007364:Intercalating Agents / Q000627:therapeutic use; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy
D000970:Antineoplastic Agents; D002843:Chromatin; D004967:Estrogens; D007364:Intercalating Agents; D003609:Dactinomycin; D004970:Estrone; D003630:Daunorubicin