INVESTIGADORES
URTREGER Alejandro Jorge
congresos y reuniones científicas
Título:
Effect of levoglucosenone and its derivatives in the malignant progression of human and murine mammary tumor cells
Autor/es:
AGOSTINA CAMMARATA; LIZETH ARIZA BAREÑO; DAMIAN DELBART; MARIA J. COSTA; AGUSTINA TARUSELLI; ANDRES BECHIS; GERMÁN GIRI; ROLANDO SPANEVELLO; LAURA B. TODARO; ALEJANDRO J. URTREGER
Lugar:
Mar del Plata
Reunión:
Congreso; LXIII Reunión Científica de la Sociedad Argentina de Investigación Clínica (SAIC); 2018
Institución organizadora:
Sociedad Argentina de Investigación Clínica (SAIC)
Resumen:
Breast cancer is a major public health problem being the second cause of cancer related death in developed countries. Conventional therapies (surgery, chemo and radiotherapy) seem to have reached a therapeutic efficacy plateau. In order to propose new therapeutic alternatives, we suggest an unexplored molecule: Levoglucosenone. Levoglucosenone results from pyrolytic treatment of microcrystalline cellulose or cellulose-containing materials, and it has been used as chiral building block for the synthesis of a wide variety of compounds with different biological activitiesNevertheless, its usefulness in oncology remains unexplored till nowadays.Here, we have evaluated the effect of levoglucosenone (compound 1) and is derivatives (compounds 2, 3 and 4) on in vitro and in vivo processes related to malignant progression using human (MDA-MB-231) and murine (LM3) mammary tumor cell lines. All compounds showed a strong antiproliferative effect, with an Inhibitory Concentration 50 (IC50) between 9 and 16 uM, obtained by MTS assay. By flow cytometry we have demonstrated an increase in the Sub G0 cell cycle fraction, compatible with the presence of apoptotic cells. Next, we studied the effect of the compounds on adhesion, migration (wound healing), invasion (transwell), and metalloproteinases (MMPs) activity (zymography). Moreover, we performed an in vivo lung colonization assay using the LM3 murine model, syngeneic in BALB/c mice. In MDA-MB-231 cells, compounds 1 and 2 reduced migratory potential while compounds 3 and 4 also reduced adhesive capacity and decreased MMP-9 secreted activity. In LM3 cells, compounds 2, 3 and 4 reduced MMP-9 activity but the compound 2also impaired invasive potential and it increased in vivo lung colonization. Based on our results, we believe that these compounds assayed could become in the future in an important alternative for breast cancer management.