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

Deniz Cansen Kahraman; Gilles Hanquet; Loïc Jeanmart; Steve Lanners; Peter Šramel; Andrej Boháč; Rengul Cetin-Atalay

doi:10.1039/c6md00392c

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

Deniz Cansen Kahraman, Gilles Hanquet, Loïc Jeanmart, Steve Lanners, Peter Šramel, Andrej Boháč, Rengul Cetin-Atalay

Unit of organic chemistry

Research output: Contribution to journal › Article › peer-review

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 μM 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 μM) 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 (A_F) 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.

Original language	English
Pages (from-to)	81-87
Number of pages	7
Journal	MedChemComm
Volume	8
Issue number	1
Early online date	7 Oct 2016
DOIs	https://doi.org/10.1039/c6md00392c
Publication status	Published - 2017

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10.1039/c6md00392c

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title = "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 μM 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 μM) 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.",

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T1 - Quinoides and VEGFR2 TKIs influence the fate of hepatocellular carcinoma and its cancer stem cells

AU - Kahraman, Deniz Cansen

AU - Hanquet, Gilles

AU - Jeanmart, Loïc

AU - Lanners, Steve

AU - Šramel, Peter

AU - Boháč, Andrej

AU - Cetin-Atalay, Rengul

PY - 2017

Y1 - 2017

N2 - 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 μM 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 μM) 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.

AB - 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 μM 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 μM) 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.

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

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

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