Ankaflavin fromMonascus-Fermented Red Rice Exhibits Selective Cytotoxic Effect and Induces Cell Death on Hep G2 Cells

We have previously shown that GSH depletion alters global metabolism of cells. In the present study, we applied a metabolomic approach for studying the early changes in metabolism in hydrogen peroxide- (H2O2-) treated hepatoma cells which were destined to die. Levels of fructose 1,6-bisphosphate and an unusual metabolite, sedoheptulose 1,7-bisphosphate (S-1,7-BP), were elevated in hepatoma Hep G2 cells. Deficiency in G6PD activity significantly reduced S-1,7-BP formation, suggesting that S-1,7-BP is formed in the pentose phosphate pathway as a response to oxidative stress. Additionally, H2O2 treatment significantly increased the level of nicotinamide adenine dinucleotide phosphate (NADP+) and reduced the levels of ATP and NAD+. Severe depletion of ATP and NAD+ in H2O2-treated Hep G2 cells was associated with cell death. Inhibition of PARP-mediated NAD+ depletion partially protected cells from death. Comparison of metabolite profiles of G6PD-deficient cells and their normal counterparts revealed that changes in GSH and GSSG per se do not cause cell death. These findings suggest that the failure of hepatoma cells to maintain energy metabolism in the midst of oxidative stress may cause cell death.

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Senescence Marker Protein-30 (SMP30) Rescues Cell Death by Enhancing Plasma Membrane Ca2+-Pumping Activity in Hep G2 Cells

Biochemical and Biophysical Research Communications ◽

10.1006/bbrc.1998.9327 ◽

1998 ◽

Vol 250 (2) ◽

pp. 374-380 ◽

Cited By ~ 70

Author(s):

Toshiko Fujita ◽

Haruhiko Inoue ◽

Tsuneo Kitamura ◽

Nobuhiro Sato ◽

Tastuo Shimosawa ◽

...

Keyword(s):

Cell Death ◽

Plasma Membrane ◽

Marker Protein ◽

Hep G2 ◽

Hep G2 Cells ◽

G2 Cells ◽

Pumping Activity

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Glutamic Acid Uptake Inhibition Assay in Cultured Hep G2 Cells as an Alternative Method for Evaluating Potential In Vivo Eye Irritation

Alternatives to Laboratory Animals ◽

10.1177/026119298901600405 ◽

1989 ◽

Vol 16 (4) ◽

pp. 344-352

Author(s):

Paul J. Dierickx

Keyword(s):

Glutamic Acid ◽

Corneal Opacity ◽

Acid Uptake ◽

Hep G2 ◽

Hep G2 Cells ◽

Eye Irritation ◽

Uptake Inhibition ◽

Range Finding ◽

G2 Cells

Glutamic acid (GA) content was measured in cultured Hep G2 cells, after treatment of the cells with test compounds. The results with 37 chemicals were compared with their respective rabbit eye irritation data, of which 17 were determined according to the OECD test, and the other 20 in range-finding studies. The chemicals were mainly organic solvents (alcohols, esters, amines, acids and others). The xenobiotics were applied to the cells for 4 hours at 5 different concentrations. The cells were then incubated for 15 minutes with tritiated GA. GA uptake inhibition was measured by liquid scintillation counting, and the results were expressed as the GI50 value, which is the concentration of test compound required to induce a 50% reduction in GA uptake. A linear correlation coefficient r = 0.66 was found between the log GI50 and the mean corneal opacity scores. This value is comparable to that obtained in total protein and uridine uptake inhibition studies. However, r = 0.81 was found when the log GI50 was compared with range-finding scores, indicating that a closer relationship exists between cytotoxicity and the latter.

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Human proapolipoprotein A-II is cleaved following secretion from Hep G2 cells by a thiol protease.

Journal of Biological Chemistry ◽

10.1016/s0021-9258(17)42584-1 ◽

1984 ◽

Vol 259 (24) ◽

pp. 15556-15563 ◽

Cited By ~ 9

Author(s):

J I Gordon ◽

H F Sims ◽

C Edelstein ◽

A M Scanu ◽

A W Strauss

Keyword(s):

Hep G2 ◽

Hep G2 Cells ◽

Thiol Protease ◽

G2 Cells

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The Hep G2 Cell Line as a Possible Alternative to Isolated Hepatocytes in Cytotoxicity Studies

Alternatives to Laboratory Animals ◽

10.1177/026119298801600105 ◽

1988 ◽

Vol 16 (1) ◽

pp. 16-22

Author(s):

Marina Marinovich ◽

Jose L. Lorenzo ◽

Liliana M. Flaminio ◽

Agnese Granata ◽

Corrado L. Galli

Keyword(s):

Cell Line ◽

Rat Hepatocytes ◽

Prostaglandin E ◽

Human Hepatoma ◽

Hep G2 ◽

Hep G2 Cells ◽

Isolated Rat Hepatocytes ◽

G2 Cells ◽

Isolated Rat

The hepatotoxicity of carbon tetrachloride (CC14) was evaluated in vitro in freshly isolated rat hepatocytes and in the human hepatoma cell line, Hep G2. Toxicity was assessed by the leakage of cytosolic enzymes (lactate dehydrogenase and aspartate aminotransferase) and cell viability (trypan blue exclusion). The established human cells were less sensitive to CCl4-induced injury; higher doses of the toxic agent and longer incubation times were necessary to elicit cell damage. Micromolar concentrations of prostaglandin E2 significantly decreased enzyme leakage in both Hep G2 cells and rat hepatocytes challenged with CC14; a stable derivative of prostacyclin (ZK 36374) was ineffective. These results suggest that human hepatoma Hep G2 cells may represent a valid alternative to isolated rat hepatocytes for an initial approach to the in vitro evaluation of cell toxicity.

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