Synergism of Small Molecules Targeting VDAC with Sorafenib, Regorafenib or Lenvatinib on Hepatocarcinoma Cell Proliferation and Survival

VENTURA C; JUNCO, M; SANTIAGO VALTIERRA FX; GOOZ M; ZHIWEI Y; TOWNSEND DM; WOSTER P; MALDONADO EN

Mar del Plata

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

Sociedad Argentina de Investigación Clínica (SAIC)

Voltage dependent anion channels (VDAC) in the outer mitochondrial membrane regulate the influx of metabolites that sustain mitochondrial metabolism. The small molecules X1 and SC18 induce mitochondrial dysfunction and cell death. X1 antagonizes the inhibitory effect of tubulin on VDAC. SC18 occupies an NADH-binding pocket in the inner wall of all VDAC isoforms. Here, we hypothesized that X1 and SC18 have a synergistic antiproliferative effect with sorafenib (Sor), regorafenib (Reg) or lenvatinib (Len), that are currently FDA-approved drugs to treat hepatocarcinoma (HCC). We used the well differentiated Huh7 and the poorly differentiated SNU-449 HCC cells to determine cell proliferation (colony formation assay), and cell survival (calcein/propidium iodide confirmed with trypan blue exclusion). Synergism was calculated by the Chou-Talalay method. A Coefficient of Interaction (CI)