New results of k- carrabiose as potential antitumor agent

BATISTA J, CALVO G, NAVARRO D, SÁENZ D, CINGOLANI R, STORTZ C, CASAS A, DI VENOSA G

Mar del Plata

Congreso; Reunión anual de sociedades de biociencias SAIC - SAB ? AAFE- AACYTAL 2023. LXVIII Reunión Científica Anual de la Sociedad Argentina de Investigación Clínica (SAIC).; 2023

Sociedad Argentina de Investigación Clínica

Carrageenans are sulfated galactans found in some red seaweeds with biological activities. In previous work, we have purified native and degraded carrageenans, including the disaccharides (carrabioses) and disaccharide-alditols as potential antitumor compounds and identified the active principle of the potential antitumor properties. -carrabiose was the most effective, showing high cytotoxic properties (IC50 0.043 ± 0.009 mg/ml), killing the murine mammary adenocarcinoma LM2 cells through an apoptotic pathway, showing a decreased motility and a decreased cell-cell and cell-matrix interactions. This work aimed to further explore the antitumor potential of -carrabiose.New results include the evaluation of the compound in a panel of tumour cell lines of various origins. The obtained IC50 values ranged from 0.051 to 0.099 mg/ml, suggesting that -carrabiose could be cytotoxic in several tissues. We also evaluated its cytotoxicity in the presence of different serum concentrations, which was not statistically different as compared to the non-serum control, showing that there are no serum enzymes degrading the compound into monosaccharides. We also evaluated -carrabiose with K+ as a counterion of the free sulfate of the compound, compared to Na+, the cation employed in the previous studies. -carrabiose did not change its cytotoxic activity, suggesting the action depends on the structure of the disaccharide and not on the counterion. Looking for a better approximation to the tumour environment, we evaluated its cytotoxicity in LM2 spheroids and, although the IC50 obtained (0.069 ± 0.02 mg/ml) was slightly higher than in the monolayer, the spheroids showed a response against the compound. These new results reinforce the idea of proposing -carrabiose as a novel antitumor agent, including using disaccharide units such as carrabioses coupled to antineoplastics to improve its cytotoxicity and antimetastatic properties.