Muscarinic modulation of paclitaxel actions on human breast cancer

2^nd World Congress on Breast Cancer

September 19-21, 2016 Phoenix, USA

Alejandro Espanol, Maria di Bari, Agustina Salem, Ilaria Cristofaro, Ada M Tata and Maria E Sales

Universidad de Buenos Aires, Argentina
Sapienza Universit�  di Roma, Italy

Scientific Tracks Abstracts: J Cancer Sci Ther

Abstract :

Cholinergic modulation of tumor progression has been described in differentexperimental models. In our laboratory, we demonstrated that long term treatment of murine mammary tumors with the non-selective agonist, carbachol (CARB) promotes cell death through the activation of muscarinic (M) receptors. We studied the effect of a combination of sub threshold doses of CARB (10-12M) with paclitaxel (PX) (10-8M) acytotoxic agent used in the treatment of breast cancer, on MDA-MB231 cells derived from a human triple negative breast tumor. The combination of CARB+PX reduced cell viability by 27�±3% (p <0.01 vs. control). In addition, the combination of the M2 selective agonist, arecaidine (ARE) (12.5 M) that promotes cell death in glioblastomas, with PX (10-9M) produced a similar reduction in cell viability (24�±7%; p<0.05) effect that was not observed with drugs added separately. By Western blot we detected the expression of M receptors (M5> M1=M2). The silencing of M2 receptor with a specific siRNA increased cell viability to control values. ARE+PX also reduced by 98.7% mRNA levels of the drug transporter ABCG2 and by 97.8% the expression of the epidermal growth factor receptor (p<0.001 vs. control). The combination did not modify the viability of MCF-10A cells derived from human normal mammary gland that do not express M receptors. These results suggest that M receptors could be considered as therapeutic targets in breast cancer and that the combination of cholinergic agonists plus cytotoxic agents, as PX may represent a novel therapeutic tool for the treatment of this illness.

Biography :

Maria E Sales is working in Centro de Estudios Farmacológicos y Botánicos (CEFYBO-CONICET), Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.

Email: malegazpio@yahoo.com.ar