Next-generation of cellulose-derived materials as a novel alternative for breast cancer treatment

ALDANA SCHEY; LIZETH ARIZA BAREÑO; LUCIANA CAÑONERO; ANDRES BECHIS; DIEGO BRITEZ NEIRA; FLORENCIA CÁMPORA; BEATRIZ E. PAVA GÓMEZ; ARIEL M. SAROTTI; ALEJANDRA SUAREZ; ROLANDO SPANEVELLO; MARCELA SOLANGE VILLAVERDE; LAURA B. TODARO; ALEJANDRO J. URTREGER

Mar del Plata

Congreso; LXVIII Reunión Científica de la Sociedad Argentina de Investigación Clínica (SAIC); 2023

Sociedad Argentina de Investigación Clínica (SAIC)

Breast cancer is a health condition that affects millions of women worldwide. In this study, a second generation of compounds derived from the pyrolytic treatment of soybean husks has been investigated as an alternative for treating this disease.Fifteen new derivatives have been explored and compared with levoglucosenone (the leading compound) in their biological activity. Only three compounds (58A, 59A, and 37D) demonstrated the capability to induce cell death, exhibiting Inhibitory Concentration 50 (IC50) values of 5.9±2, 5.4±3, and 7.2±4 uM, for LM3 cells respectively. These values were notably lower than levoglucosenones, making them promising candidates. Next, we investigated signaling pathways related to cell proliferation and survival. Western blot assays, revealed that 59A led to an inhibition of the ERK/MAPK pathway and an increase in apoptotic markers expression.In order to propose an improved therapy, we evaluated the combined effect with the chemotherapeutic agent doxorubicin. Doxorubicin showed an IC50 of 0.06 uM, but its combination did not generate a synergistic or additive effect. In a second stage, we combined the compounds with metabolism modulators, since all compounds induce an increase in glucose consumption and lactate production. We employed 2-deoxyglucose (2-DG: a glucose analog that inhibits glycolysis), 6-aminonicotinamide (6-AM: an antimetabolite that inhibits the pentose phosphate pathway) and metformin (a glucose levels modulator). Interestingly, only 2-DG significantly increased levoglucosenone-derivatives’ effect . Loewe curves, from Combenefit software, described this interaction as a synergistic.Based on our findings, cellulose-derived materials demonstrate a promising biological profile, positioning them as an alternative for breast cancer management. These materials have the potential to be used either as standalone therapies or to enhance the effect of pre-existing therapies.