Antiproliferative Effects of Oxytocin and Desmopressin on Canine Mammary Cancer Cells

Abstract

Neoplasms of the mammary gland represent the most frequent tumor type in the female dog, and according to the histologic criteria, approximately 50% of them are malignant. In the most aggressive cases of mammary cancer, surgery is not enough to warrant a favorable outcome, and adjuvant therapies are needed to improve the patient’s overall survival. The aim of the present study was to evaluate the effects of two peptides on proliferation of a canine mammary cancer cell line derived from a simple carcinoma. The cell line CMT-U27 was grown in 96-well plates, at two cell densities (4 × 103 and 8 × 103 cells/well). Cultures were treated with oxytocin (OT) or desmopressin at five concentrations (10, 50, 100, 500, and 1000 nM). After 72 h of incubation, cell proliferation was determined by the MTT assay. Results showed that with 4 × 103 cells/well, OT at 50, 500, and 1000 nM was growth inhibitory for the cells, being statistically significant at 1000 nM. On the contrary, no antiproliferative effect was observed with 10 or 100 nM. At 8 × 103 cells/well, OT showed a significant antiproliferative effect only with the highest concentration (1000 nM). Desmopressin at 4 × 103 cells/well decreased cell viability at concentrations of 50, 100, 500, and 1000 nM (statistically significant with the highest concentration), while no effect was observed with 10 nM. With 8 × 103 cells/well, this peptide reduced cell growth at 100, 500, and 1000 nM. In conclusion, we suggest that these peptides may be potential and promising compounds for the treatment of dogs with simple carcinomas of the mammary gland. In vivo studies are required to confirm this hypothesis.

From Conventional to Precision Therapy in Canine Mammary Cancer: A Comprehensive Review

“…Oxytocin is a peptide hormone mainly synthesized in the hypothalamus that plays a role in uterine contraction and milk ejection, among other functions, and has been linked to the mammary carcinogenic process. Human ( 129 ) and canine ( 130 ) carcinoma cell lines and HBC xenografted mice ( 131 ) have shown reduced proliferation after oxytocin treatment. Recently, it has been shown that the expression of oxytocin receptors in CMTs is associated with ER+, benign tumors, and low-grade malignant tumors compared to high-grade malignant tumors ( 132 ).…”

“…In oncology, a number of studies have shown in mouse models of HBC and in different HBC cell lines that this peptide seems to have anti-metastatic and anti-proliferative effects, probably by targeting V2R-expressing cancer cells and raising intracellular cAMP ( 136 , 137 ). In a study on canine mammary carcinoma cell lines, desmopressin was shown to decrease cell viability at high concentrations ( 130 ). Furthermore, a veterinary clinical trial has demonstrated that the perioperative administration of desmopressin increases the DFI and OS in CMC ( 138 ).…”

Oxytocin and cancer: An emerging link

“…Interestingly, subsequent studies have shown that oxytocin in fact inhibits proliferation of breast cancer cell lines, such as MDA-MB231, MCF7, and T47D[ 55 , 56 ], as well as the canine mammary cell line CMT-U27[ 57 ], mouse mammary carcinoma cell line TS/A, and rat mammary carcinoma cell line D-R3230AC[ 9 ]. This effect was shown to be mediated via the cyclic adenosine monophosphate protein kinase A in human cell lines[ 58 ].…”

Effect of perioperative desmopressin in cats with mammary carcinoma treated with bilateral mastectomy

“…14 Additionally, application of desmopressin at a concentration of 1000 nM to canine mammary cancer cells resulted in a decrease in cell proliferation by 22%. 21 However, to the authors' knowledge, there are no studies examining the efficacy or safety of desmopressin usage in cats.…”