URTREGER Alejandro Jorge
congresos y reuniones científicas
New drugs for cancer treatment. Effect of norcantharidin and levoglucosenone on malignant progression of human and murine mammary tumor cells
LIZETH ARIZA BAREÑO; AGOSTINA CAMMARATA; MARIA J. COSTA; GERMÁN GIRI; ROLANDO SPANEVELLO; ALEJANDRA SUAREZ; LAURA B. TODARO; ALEJANDRO J. URTREGER
Cdad Autonoma de Buenos Aires
Congreso; Segunda Reunión Conjunta de Sociedades de BioCiencias; 2017
Sociedad Argentina de Investigación Clínica (SAIC)
In the present work, we start the evaluation of norcantharidin (NCTD) and levoglucosenone (Levo) on in vitro processes associated to malignant progression, using human and murine mammary tumor-derived cell lines.Levo results from pyrolytic treatment of microcrystalline cellulose or cellulose-containing materials, and it has been used as the basis for the synthesis of a wide variety of compounds with different biological activities. Although it was shown that it could alter the cell cycle, its usefulness in oncology remains unexplored till nowadays. NCTD is a less toxic and demethylated form of cantharidin, an active constituent of Mylabris beetle, used in traditional Chinese medicine.The effect of NCTD was analyzed on the triple negative mammary cell lines 4T1 and Hs578T, while the effect of Levo was analyzed on LM3 and MDA-MB231 cell lines. Both drugs proved to have a strong antiproliferative effect. NCTD exhibited an IC50 of 35 and 55 uM for 4T1 and HS578T cells respectively. In the case of Levo, the IC50 was 10 uM for the two cell lines analyzed. By flow cytometry we have determined that both drugs induced an increase in the sub-G1 fraction of the cell cycle, compatible with the presence of apoptotic cells. Related to in vitro malignant progression, we studied adhesion, migration (by wound healing assays) and secreted matrix metalloproteinases activity (by zymography) in all cell lines mentioned above, treated or not with both drugs. A significant reduction in all parameters associated to tumor progression was observed in a dose-dependent manner.The important response to the treatments observed in vitro, suggests that these drugs could be useful for in vivo assays, hoping that in the future they could be suitable for breast cancer treatment.