NEW RESULTS ON K-CARRABIOSE AS POTENTIAL ANTITUMOR AGENT

BATISTA, J; CALVO, G; NAVARRO, D; SAENZ, D; CINGOLANI, R; STORZT, C; CASAS, A; DI VENOSA, G

Mar del Plata, Provincia de Buenos Aires,

Congreso; Reunión Anual de Sociedades de Biociencias; 2023

Sociedad Argentina de Investigación Clínica (SAIC),

Carrageenans are sulfatedgalactans 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 andidentified the active principle of the potential antitumor properties. k-carrabiose was themost effective, showing high cytotoxic properties (IC50 0.043 ± 0.009 mg/ml),killing the murine mammary adenocarcinoma LM2 cells through an apoptoticpathway, showing a decreased motility and a decreased cell-cell and cell-matrixinteractions. This work aimed to further explore the antitumor potential of k-carrabiose.New results include the evaluationof the compound in a panel of tumour cell lines of various origins. Theobtained IC50 values ranged from 0.051 to 0.099 mg/ml, suggesting that k-carrabiose could becytotoxic in several tissues. We also evaluated its cytotoxicity in thepresence of different serum concentrations, which was not statisticallydifferent as compared to the non-serum control, showing that there are no serumenzymes degrading the compound into monosaccharides. We also evaluated k-carrabiose with K+as a counterion of the free sulfate of the compound, compared to Na+,the cation employed in the previous studies. k-carrabiose did notchange its cytotoxic activity, suggesting the action depends on the structureof the disaccharide and not on the counterion. Looking for a betterapproximation to the tumour environment, we evaluated its cytotoxicity in LM2 spheroidsand, although the IC50 obtained (0.069 ± 0.02 mg/ml) was slightly higher thanin the monolayer, the spheroids showed a response against the compound. These new results reinforce theidea of proposing k-carrabiose as a novel antitumor agent, including usingdisaccharide units such as carrabioses coupled to antineoplastics to improveits cytotoxicity and antimetastatic properties.