title: In vitro synergism between estrogens and cytotoxic agents.
abstract: 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.
mesh_terms: 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
chemical_list: D000970:Antineoplastic Agents; D002843:Chromatin; D004967:Estrogens; D007364:Intercalating Agents; D003609:Dactinomycin; D004970:Estrone; D003630:Daunorubicin