ABSTRACT
Furoxan derivatives with in vitro cytotoxic activity were investigated as antitumoral agents in vivo. The compounds were tested in murine models of both CCRFS-180 II sarcoma and mammary adenocarcinoma. Two of the furoxan derivatives considered here, 3-formyl-4-phenyl-1,2,5-oxadiazole N2-oxide and 3-carbonitrile-4-phenyl-1,2,5-oxadiazole N2-oxide, present in vivo antitumoral activity. They were able to produce more than 90% of tumoral necrosis under the experimental protocol of administration and posology employed. NO-releasing capacity of furoxans may explain the anti-neoplastic activity of these compounds.
Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Oxadiazoles/chemical synthesis , Oxadiazoles/pharmacology , Animals , Antineoplastic Agents/toxicity , Cell Line, Tumor , Chemical Phenomena , Chemistry, Pharmaceutical , Chemistry, Physical , Female , Mammary Neoplasms, Experimental/drug therapy , Mammary Neoplasms, Experimental/pathology , Mice , Mice, Inbred BALB C , Neoplasm Transplantation , Oxadiazoles/toxicity , Quinoxalines/pharmacology , Sarcoma, Experimental/drug therapy , Sarcoma, Experimental/pathologyABSTRACT
The effect of oxytocin on uterine estrogen and progesterone receptors (ER and PgR) was investigated in vivo in groups of immature female rats that were treated subcutaneously with oxytocin, 0.5 or 5 IU (1 and 10 micrograms) for 5 and 3 d, respectively. Receptor concentrations and affinities were estimated by Scatchard analysis, using radioactive hormones as ligands. Statistical analysis was performed by Student's t test and by ANOVA. Oxytocin did not alter the receptor affinity for either steroid hormone, but the lower dose significantly decreased the concentrations of receptors: ER = 486 +/- 76 fmol/mg vs 346 +/- 105 fmol/mg (P < 0.001) and PgR = 686 +/- 237 fmol/mg vs 433 +/- 236 fmol/fmol/mg (P < 0.01) (mean +/- SD values for control and treated animals, respectively). There were no significant effects on the plasma 17 beta-E and Pg concentrations. In in vitro studies with mature rats, uterine specific binding of estradiol and progesterone in the presence or the absence of oxytocin showed no modification. Oxytocin could be a negative modulator of ER and PgR in the uterus, even though the mechanism of its action remains unknown. It could have potential implications on reproductive capacity and fertilization.
