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Antineoplastic effects of gamma linolenic Acid on hepatocellular carcinoma cell lines.

Itoh S, Taketomi A, Harimoto N, Tsujita E, Rikimaru T, Shirabe K, Shimada M, Maehara Y - J Clin Biochem Nutr (2010)

Bottom Line: Cell proliferation and reactive oxygen species (ROS) generation including lipid peroxidation and apoptosis were compared.GLA treatment significantly reduced cell proliferation, generated ROS, and induced apoptosis.Furthermore, chromium mesoporphyrin (CrMP), an inhibitor of HO activity, significantly potentiated GLA cytotoxicity.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan.

ABSTRACT
The aim of this study was to investigate the effect and the mechanism of gamma linolenic acid (GLA) treatment on human hepatocellular (HCC) cell lines. The human HCC cell line HuH7 was exposed to GLA. Cell proliferation and reactive oxygen species (ROS) generation including lipid peroxidation and apoptosis were compared. We then used a cDNA microarray analysis to investigate the molecular changes induced by GLA. GLA treatment significantly reduced cell proliferation, generated ROS, and induced apoptosis. After 24 h exposure of Huh7 cells to GLA, we identified several genes encoding the antioxidant proteins to be upregulated: heme oxygenase-1 (HO-1), aldo-keto reductase 1 family C1 (AKR1C1), C4 (AKR1C4), and thioredoxin (Trx). The HO-1 protein levels were overexpressed in Huh7 cells after GLA exposure using a Western blot analysis. Furthermore, chromium mesoporphyrin (CrMP), an inhibitor of HO activity, significantly potentiated GLA cytotoxicity. GLA treatment has induced cell growth inhibition, ROS generation including lipid peroxidation, and HO-1 production for antioxidant protection against oxidative stress caused by GLA in Huh7 cells. GLA treatment should be considered as a therapeutic modality in patients with advanced HCC.

No MeSH data available.


Related in: MedlinePlus

GLA induced the decrease in mitochondrial membrane potential in Huh7 cells. Huh7 cells were untreated (Control) or treated with 250 µM GLA (GLA) for 12 h. Mitochondrial membrane potential was detedcted by flow cytometry analysis using Rh123 and PI.
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Figure 3: GLA induced the decrease in mitochondrial membrane potential in Huh7 cells. Huh7 cells were untreated (Control) or treated with 250 µM GLA (GLA) for 12 h. Mitochondrial membrane potential was detedcted by flow cytometry analysis using Rh123 and PI.

Mentions: Since the ROS can lead to damage of mitochondria, we assessed mitochondrial membrane potential by flow cytometry after double staining with Rh123 and PI. Rh123 is selectively taken up by mitochondria, directly proportional to mitochondria membrane potential. PI is imported into cells and binds to cellular DNA when the integrity of the plasma membrane is lost. Fig. 3 shows flow cytometric histograph of Huh7 cells treated with GLA for 12 h. Untreated Huh7 cells were predominantly located in the PI-negative and Rh123-positive field (lower right quadrant), reflective of viable cells. The percentage of cells in the PI and Rh123-negative field (lower left quadrant), reflecting cells that are still viable but with damaged mitochondria, was increased by GLA treatment up to 32%. The percentage of cells in the PI positive field was more increased by GLA for 24 h (data not shown).


Antineoplastic effects of gamma linolenic Acid on hepatocellular carcinoma cell lines.

Itoh S, Taketomi A, Harimoto N, Tsujita E, Rikimaru T, Shirabe K, Shimada M, Maehara Y - J Clin Biochem Nutr (2010)

GLA induced the decrease in mitochondrial membrane potential in Huh7 cells. Huh7 cells were untreated (Control) or treated with 250 µM GLA (GLA) for 12 h. Mitochondrial membrane potential was detedcted by flow cytometry analysis using Rh123 and PI.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2901768&req=5

Figure 3: GLA induced the decrease in mitochondrial membrane potential in Huh7 cells. Huh7 cells were untreated (Control) or treated with 250 µM GLA (GLA) for 12 h. Mitochondrial membrane potential was detedcted by flow cytometry analysis using Rh123 and PI.
Mentions: Since the ROS can lead to damage of mitochondria, we assessed mitochondrial membrane potential by flow cytometry after double staining with Rh123 and PI. Rh123 is selectively taken up by mitochondria, directly proportional to mitochondria membrane potential. PI is imported into cells and binds to cellular DNA when the integrity of the plasma membrane is lost. Fig. 3 shows flow cytometric histograph of Huh7 cells treated with GLA for 12 h. Untreated Huh7 cells were predominantly located in the PI-negative and Rh123-positive field (lower right quadrant), reflective of viable cells. The percentage of cells in the PI and Rh123-negative field (lower left quadrant), reflecting cells that are still viable but with damaged mitochondria, was increased by GLA treatment up to 32%. The percentage of cells in the PI positive field was more increased by GLA for 24 h (data not shown).

Bottom Line: Cell proliferation and reactive oxygen species (ROS) generation including lipid peroxidation and apoptosis were compared.GLA treatment significantly reduced cell proliferation, generated ROS, and induced apoptosis.Furthermore, chromium mesoporphyrin (CrMP), an inhibitor of HO activity, significantly potentiated GLA cytotoxicity.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan.

ABSTRACT
The aim of this study was to investigate the effect and the mechanism of gamma linolenic acid (GLA) treatment on human hepatocellular (HCC) cell lines. The human HCC cell line HuH7 was exposed to GLA. Cell proliferation and reactive oxygen species (ROS) generation including lipid peroxidation and apoptosis were compared. We then used a cDNA microarray analysis to investigate the molecular changes induced by GLA. GLA treatment significantly reduced cell proliferation, generated ROS, and induced apoptosis. After 24 h exposure of Huh7 cells to GLA, we identified several genes encoding the antioxidant proteins to be upregulated: heme oxygenase-1 (HO-1), aldo-keto reductase 1 family C1 (AKR1C1), C4 (AKR1C4), and thioredoxin (Trx). The HO-1 protein levels were overexpressed in Huh7 cells after GLA exposure using a Western blot analysis. Furthermore, chromium mesoporphyrin (CrMP), an inhibitor of HO activity, significantly potentiated GLA cytotoxicity. GLA treatment has induced cell growth inhibition, ROS generation including lipid peroxidation, and HO-1 production for antioxidant protection against oxidative stress caused by GLA in Huh7 cells. GLA treatment should be considered as a therapeutic modality in patients with advanced HCC.

No MeSH data available.


Related in: MedlinePlus