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Quinoides and VEGFR2 TKIs influence the fate of hepatocellular carcinoma and its cancer stem cells.

ABSTRACT: Bioactivities of quinoides 1-5 and VEGFR2 TKIs 6-10 in hepatocellular cancer (HCC) and cancer stem cells (HCSCs) were studied. The compounds exhibited IC50 values in ?M concentrations in HCC cells. Quinoide 3 was able to eradicate cancer stem cells, similar to the action of the stem cell inhibitor DAPT. However, the more cytotoxic VEFGR TKIs (IC50: 0.4-3.0 ?M) including sorafenib, which is the only FDA approved drug for the treatment of HCC, enriched the hepatocellular cancer stem cell population by 2-3 fold after treatment. An aggressiveness factor (AF) was proposed to quantify the characteristics of drug candidates for their ability to eradicate the CSC subpopulation. Considering the tumour heterogeneity and marker positive cancer stem cell like subpopulation enrichment upon treatments in patients, this study emphasises the importance of the chemotherapeutic agent choice acting differentially on all the subpopulations including marker-positive CSCs.

SUBMITTER: Kahraman DC 

PROVIDER: S-EPMC6072489 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Quinoides and VEGFR2 TKIs influence the fate of hepatocellular carcinoma and its cancer stem cells.

Kahraman Deniz Cansen DC   Hanquet Gilles G   Jeanmart Loïc L   Lanners Steve S   Šramel Peter P   Boháč Andrej A   Cetin-Atalay Rengul R  

MedChemComm 20161007 1

Bioactivities of quinoides <b>1-5</b> and VEGFR2 TKIs <b>6-10</b> in hepatocellular cancer (HCC) and cancer stem cells (HCSCs) were studied. The compounds exhibited IC<sub>50</sub> values in μM concentrations in HCC cells. Quinoide <b>3</b> was able to eradicate cancer stem cells, similar to the action of the stem cell inhibitor <b>DAPT</b>. However, the more cytotoxic VEFGR TKIs (IC<sub>50</sub>: 0.4-3.0 μM) including sorafenib, which is the only FDA approved drug for the treatment of HCC, enri  ...[more]

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