scholarly journals A hexokinase isoenzyme switch in human liver cancer cells promotes lipogenesis and enhances innate immunity

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Laure Perrin-Cocon ◽  
Pierre-Olivier Vidalain ◽  
Clémence Jacquemin ◽  
Anne Aublin-Gex ◽  
Keedrian Olmstead ◽  
...  
Keyword(s):  
Cell Line ◽  
Glycogen Storage ◽  
Central Carbon Metabolism ◽  
Metabolic Reprogramming ◽  
Innate Immune Responses ◽  
Metabolic Functions ◽  
Rate Limiting Step ◽  
Human Liver Cancer ◽  
Functional Consequences ◽  
Human Liver Cancer Cells

AbstractDuring the cancerous transformation of normal hepatocytes into hepatocellular carcinoma (HCC), the enzyme catalyzing the first rate-limiting step of glycolysis, namely the glucokinase (GCK), is replaced by the higher affinity isoenzyme, hexokinase 2 (HK2). Here, we show that in HCC tumors the highest expression level of HK2 is inversely correlated to GCK expression, and is associated to poor prognosis for patient survival. To further explore functional consequences of the GCK-to-HK2 isoenzyme switch occurring during carcinogenesis, HK2 was knocked-out in the HCC cell line Huh7 and replaced by GCK, to generate the Huh7-GCK+/HK2− cell line. HK2 knockdown and GCK expression rewired central carbon metabolism, stimulated mitochondrial respiration and restored essential metabolic functions of normal hepatocytes such as lipogenesis, VLDL secretion, glycogen storage. It also reactivated innate immune responses and sensitivity to natural killer cells, showing that consequences of the HK switch extend beyond metabolic reprogramming.

scholarly journals Lipogenesis and innate immunity in hepatocellular carcinoma cells reprogrammed by an isoenzyme switch of hexokinases

2020 ◽  
Author(s):  
Laure Perrin-Cocon ◽  
Pierre-Olivier Vidalain ◽  
Clémence Jacquemin ◽  
Anne Aublin-Gex ◽  
Keedrian Olmstead ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Line ◽  
Glycogen Storage ◽  
Central Carbon Metabolism ◽  
Metabolic Reprogramming ◽  
Innate Immune Responses ◽  
Metabolic Functions ◽  
Rate Limiting Step ◽  
Functional Consequences ◽  
Rate Limiting

AbstractDuring the cancerous transformation of normal hepatocytes into hepatocellular carcinoma (HCC), the enzyme catalyzing the first rate-limiting step of glycolysis, namely the glucokinase (GCK), is replaced by the higher affinity isoenzyme, hexokinase 2 (HK2). The transcriptomic analysis of HCC tumors shows that highest expression level of HK2 in tumor lesions is inversely correlated to GCK expression, and is associated to poor prognosis for patient survival. To further explore functional consequences of the GCK-to-HK2 isoenzyme switch occurring during carcinogenesis, HK2 was knocked-out in the HCC cell line Huh7 and replaced by GCK, to generate the Huh7-GCK+/HK2− cell line. HK2 knockdown and GCK expression rewired central carbon metabolism, stimulated mitochondrial respiration and restored essential metabolic functions of normal hepatocytes such as lipogenesis, VLDL secretion, glycogen storage. It also reactivated innate immune responses and sensitivity to natural killer cells, showing that consequences of the HK switch extend beyond metabolic reprogramming.

scholarly journals Novel piperazine core compound induces death in human liver cancer cells: possible pharmacological properties

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Nima Samie ◽  
Sekaran Muniandy ◽  
M. S. Kanthimathi ◽  
Batoul Sadat Haerian ◽  
Raja Elina Raja Azudin
Keyword(s):  
Liver Cancer ◽  
Cancer Cells ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Cell ◽  
Human Liver ◽  
Liver Cancer Cell ◽  
Liver Cancer Cells ◽  
Human Liver Cancer ◽  
Human Liver Cancer Cells

Abstract The current study evaluates the cytotoxic mechanism of a novel piperazine derivate designated as PCC against human liver cancer cells. In this context, human liver cancer cell lines, SNU-475 and 243, human monocyte/macrophage cell line, CRL-9855, and human B lymphocyte cell line, CCL-156, were used to determine the IC50 of PCC using the standard MTT assay. PCC displayed a strong suppressive effect on SNU-475 and SNU-423 cells with an IC50 value of 6.98 ± 0.11 μg/ml and 7.76 ± 0.45 μg/ml respectively, after 24 h of treatment. Significant dipping in the mitochondrial membrane potential and elevation in the released of cytochrome c from the mitochondria indicated the induction of the intrinsic apoptosis pathway by PCC. Activation of this pathway was further evidenced by significant activation of caspase 3/7 and 9. PCC was also shown to activate the extrinsic pathways of apoptosis via activation of caspase-8 which is linked to the suppression of NF-ƙB translocation to the nucleus. Cell cycle arrest in the G1 phase was confirmed by flow cytometry and up-regulation of glutathione reductase expression was quantified by qPCR. This study suggests that PCC is a simultaneous inducer of intrinsic and extrinsic pathways of apoptosis in liver cancer cell lines.

Precise Electrical Detection of Curcumin Cytotoxicity in Human Liver Cancer Cells

2021 ◽  
Author(s):  
Novi Angeline ◽  
Sung-Sik Choo ◽  
Cheol-Hwi Kim ◽  
Suk Ho Bhang ◽  
Tae-Hyung Kim
Keyword(s):  
Liver Cancer ◽  
Cancer Cells ◽  
Human Liver ◽  
Electrical Detection ◽  
Liver Cancer Cells ◽  
Human Liver Cancer ◽  
Human Liver Cancer Cells

scholarly journals Aberrant miRNA expression response to UV irradiation in human liver cancer cells

2014 ◽  
Vol 9 (3) ◽  
pp. 904-910 ◽  
Author(s):  
GAOFENG LIANG ◽  
GUANGDA LI ◽  
YANYAN WANG ◽  
WANJUN LEI ◽  
ZHONGDANG XIAO
Keyword(s):  
Liver Cancer ◽  
Cancer Cells ◽  
Uv Irradiation ◽  
Mirna Expression ◽  
Human Liver ◽  
Liver Cancer Cells ◽  
Human Liver Cancer ◽  
Expression Response ◽  
Human Liver Cancer Cells

scholarly journals Formulation, Characterization and Biological Activity Screening of Sodium Alginate-Gum Arabic Nanoparticles Loaded with Curcumin

Molecules ◽  
2020 ◽  
Vol 25 (9) ◽  
pp. 2244 ◽  
Author(s):  
Abdelkader Hassani ◽  
Syed Mahmood ◽  
Hamid Hammad Enezei ◽  
Siti Aslina Hussain ◽  
Hamad Ali Hamad ◽  
...  
Keyword(s):  
Sodium Alginate ◽  
Radical Scavenging ◽  
Chemical Characterization ◽  
Gum Arabic ◽  
Mcf7 Cells ◽  
Scanning Calorimetry ◽  
Anticancer Properties ◽  
Transmission Electron ◽  
Human Liver Cancer ◽  
Human Liver Cancer Cells

The approach of drug delivery systems emphasizes the use of nanoparticles as a vehicle, offering the optional property of delivering drugs as a single dose rather than in multiple doses. The current study aims to improve antioxidant and drug release properties of curcumin loaded gum Arabic-sodium alginate nanoparticles (Cur/ALG-GANPs). The Cur/ALG-GANPs were prepared using the ionotropic gelation technique and further subjected to physico-chemical characterization using attenuated total reflectance–Fourier transform infrared (ATR-FTIR), X-ray diffractometry (XRD), differential scanning calorimetry (DSC), size distribution, and transmission electron microscopy (TEM). The size of Cur/ALG-GANPs ranged between 10 ± 0.3 nm and 190 ± 0.1 nm and the zeta potential was –15 ± 0.2 mV. The antioxidant study of Cur/ALG-GANPs exhibited effective radical scavenging capacity for 1,1-diphenyl-2-picrylhydrazyl (DPPH) at concentrations that ranged between 30 and 500µg/mL. Cytotoxicity was performed using MTT assay to measure their potential in inhibiting the cell growth and the result demonstrated a significant anticancer activity of Cur/ALG-GANPs against human liver cancer cells (HepG2) than in colon cancer (HT29), lung cancer (A549) and breast cancer (MCF7) cells. Thus, this study indicates that Cur/ALG-GANPs have promising anticancer properties that might aid in future cancer therapy.

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