Study of the antineoplastic activity of products derived from cellulose-containing materials

DAMIAN DELBART; LIZETH ARIZA BAREÑO; MARIA J. COSTA; AGUSTINA TARUSELLI; ANDRES BECHIS; GERMÁN GIRI; ROLANDO SPANEVELLO; MARCELA VILLAVERDE; LAURA B. TODARO; ALEJANDRO J. URTREGER

Mar del Plata

Congreso; LXIV Reunión Científica de la Sociedad Argentina de Investigación Clínica (SAIC); 2019

Sociedad Argentina de Investigación Clínica (SAIC)

Breast cancer is a major public health problem being the second cause of cancer related death in developed countries. In order to propose new treatment alternatives, we have explored the effect of Levoglucosenone and its derivatives in preclinical settings. Levoglucosenone results from pyrolytic treatment of cellulose-containing materials, and it has been used for the synthesis of compounds with different biological activities but its usefulness in oncology remains unexplored. Here, we have evaluated the effect of levoglucosenone (compound 1) and is derivatives (compounds 2, 3 and 4) on human (MCF7) and murine (LM3) mammary tumor cell lines.All compounds showed a strong antiproliferative effect, with an Inhibitory Concentration 50 (IC50) of 50 and 12 uM for MCF7 and LM3 respectively. Since through flow cytometry we observed only a slight increase in the sub-G0 fraction of the cell cycle, we decide to study the mechanisms involved in the reduced cell number observed. First, we analyzed the effect on senescence (b-gal assay) and autophagy (Beclin I and LC3 expression). No modulation of both processes could be detected even after 72 h retreatment. Using the fluorophore (TMRM) we observed that the compounds induce the loss of mitochondrial membrane potential which could lead to the intrinsic apoptosis pathway. Moreover, as an energetic compensatory process, a 2-fold increase of glucose consumption and lactate production was detected (p 0.05 Anova). Finally, in vivo studies employing LM3 cells were performed to evaluate whether the pre-treatment with the compounds has an effect on lung colonization. Compounds 1 and 2 highly reduced lung metastasis, [median (range): 2,5 (0-10) and 7 (3-8) respectively]. While compounds 3 and 4 had no effect as compared to control treatment [median (range): 58 (12-70), p 0.05 Kruskal-Wallis test]. Based on our results, we believe that our compounds could become in the future an important alternative for breast cancer management.