phomopsin and Breast-Neoplasms

The influences of two toxins, phomopsin and ivalin, which are reported to exhibit carcinogenic and antitumor activities, respectively, were studied on steroid hormone receptor binding. A mycotoxic carcinogenic fraction A (phomopsin) was isolated from Phomopsis leptostromiformis. The antitumor sesquiterpene lactone ivalin was obtained from the "vomiting bush" Geigeria. Competitive binding analyses were conducted with radiolabeled steroid ligands and unlabeled toxins. No effect of these toxins was observed on either the binding capacity or on the rate of steroid association of [3H]-estradiol-17 beta, [3H]promegestone (R5020), and [3H]dexamethasone to their respective receptors in cytosol of human breast cancer and rat liver. The concentrations of phomopsin and ivalin varied between 0.85 nM to 14 micron in the competitive binding assays. These data suggest the carcinogenic and antitumor activities of these toxins do not involve association with steroid hormone receptors.

Topics: Animals; Breast Neoplasms; Female; Humans; In Vitro Techniques; Lactones; Ligands; Liver; Male; Mycotoxins; Rats; Rats, Inbred F344; Receptors, Estrogen; Receptors, Glucocorticoid; Receptors, Progesterone; Receptors, Steroid; Sesquiterpenes; Time Factors; Tritium

Ivalin is a plant alkaloid that inhibits the induction of tumors in animals. Phomopsin is a mycotoxin known to be carcinogenic. To determine if these compounds influence endocrine responsiveness, their effect on steroid receptors was measured. Neither of these toxins had a direct effect on either the binding capacity or the rate of steroid association of [3H]estradiol-17 beta, [3H]R5020, or [3H]dexamethasone to their respective receptors in cytosol of human breast cancer and rat liver. However, steroid receptor levels of MCF-7 cells, grown in tissue culture, were altered by ivalin and phomopsin. Ivalin at 10(-6) M depressed estrogen receptor levels, while glucocorticoid receptor levels were increased. At 10(-6) M, phomopsin was inhibitory of both progestin and glucocorticoid binding capacities. Data obtained from the proliferation of MCF-7 cells indicated that ivalin and phomopsin at 10(-6) M decreased the number of cells grown in tissue culture. Phomopsin exhibited an inhibitory effect on both [3H]thymidine and [3H]glycine incorporation, while ivalin stimulated [3H]glycine incorporation.

Topics: Antineoplastic Agents; Breast Neoplasms; Cell Division; Cell Survival; Cells, Cultured; Dexamethasone; Estradiol; Female; Glycine; Humans; Lactones; Mycotoxins; Promegestone; Receptors, Steroid; Sesquiterpenes; Thymidine; Tritium