Combined arginine and ascorbic acid treatment induces apoptosis in the hepatoma cell line HA22T/VGH and changes in redox status involving the pentose phosphate pathway and reactive oxygen and nitrogen species☆

Hsieh, Bau-Shan; Huang, Liwen; Su, Shu-Jem; Cheng, Hsiao-Ling; Hu, Yue; Hung, Thu-Ching; Chang, Kee-Lung

doi:10.1016/j.jnutbio.2010.01.009

Cited by 25 publications

(22 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Avemar, a fermented extract of wheat germ with antimetastatic effects in various human tumors, has been proposed to elicit apoptosis in Jurkat T cells by decreasing G6PD and TKTL activity [116]. A combination of arginine and ascorbic acid induces apoptosis in the human hepatoma cell line HA22T/VGH, by inhibiting the activities of G6PD, 6PGD, and TA [117]. Ascorbic acid, although under physiological conditions known to function as an antioxidant by directly reacting with ROS, also has pro-oxidant properties, because in many cells, such as blood cells and tumor cell lines [118], it can be taken up as dehydroascorbic acid and then recycled into ascorbic acid using the intracellular GSH as a reducing agent [119]: this activates the PPP [29].…”

Section: The Ppp and Tumor Cell Deathmentioning

confidence: 99%

“…Ascorbic acid, although under physiological conditions known to function as an antioxidant by directly reacting with ROS, also has pro-oxidant properties, because in many cells, such as blood cells and tumor cell lines [118], it can be taken up as dehydroascorbic acid and then recycled into ascorbic acid using the intracellular GSH as a reducing agent [119]: this activates the PPP [29]. Because in a paper of Hsieh et al [117] ascorbic acid had no effect on the enzymatic activity of G6PD if used alone, but inhibited G6PD only in combination with arginine, when the synthesis of NO is markedly increased, it is likely that ascorbic acid decreases the PPP flux by an indirect mechanism, for instance by increasing the production of NO: it has been recently observed by some of us that NO is an inhibitor of G6PD and PPP flux [24].…”

Section: The Ppp and Tumor Cell Deathmentioning

confidence: 99%

See 1 more Smart Citation

The pentose phosphate pathway: An antioxidant defense and a crossroad in tumor cell fate

Riganti

Gazzano

Polimeni

et al. 2012

Free Radical Biology and Medicine

346

289

View full text Add to dashboard Cite

Section: The Ppp and Tumor Cell Deathmentioning

confidence: 99%

Section: The Ppp and Tumor Cell Deathmentioning

confidence: 99%

The pentose phosphate pathway: An antioxidant defense and a crossroad in tumor cell fate

Riganti

Gazzano

Polimeni

et al. 2012

Free Radical Biology and Medicine

346

289

View full text Add to dashboard Cite

“…Since cancer cells generally have higher levels of reactive oxygen species, it appears that the additional oxidative stress imposed by AA cannot be ameliorated by cellular antioxidant responses and cell death is triggered [36]. Several studies have shown that combinations of AA with other anticancer agents often exhibit enhanced cytotoxicity [34], [37]–[40].…”

Section: Introductionmentioning

confidence: 99%

Ascorbic Acid and a Cytostatic Inhibitor of Glycolysis Synergistically Induce Apoptosis in Non-Small Cell Lung Cancer Cells

et al. 2013

View full text Add to dashboard Cite

Ascorbic acid (AA) exhibits significant anticancer activity at pharmacologic doses achievable by parenteral administration that have minimal effects on normal cells. Thus, AA has potential uses as a chemotherapeutic agent alone or in combination with other therapeutics that specifically target cancer-cell metabolism. We compared the effects of AA and combinations of AA with the glycolysis inhibitor 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3-PO) on the viability of three non-small cell lung cancer (NSCLC) cell lines to the effects on an immortalized lung epithelial cell line. AA concentrations of 0.5 to 5 mM caused a complete loss of viability in all NSCLC lines compared to a <10% loss of viability in the lung epithelial cell line. Combinations of AA and 3-PO synergistically enhanced cell death in all NSCLC cell lines at concentrations well below the IC50 concentrations for each compound alone. A synergistic interaction was not observed in combination treatments of lung epithelial cells and combination treatments that caused a complete loss of viability in NSCLC cells had modest effects on normal lung cell viability and reactive oxygen species (ROS) levels. Combination treatments induced dramatically higher ROS levels compared to treatment with AA and 3-PO alone in NSCLC cells and combination-induced cell death was inhibited by addition of catalase to the medium. Analyses of DNA fragmentation, poly (ADP-ribose) polymerase cleavage, annexin V-binding, and caspase activity demonstrated that AA-induced cell death is caused via the activation of apoptosis and that the combination treatments caused a synergistic induction of apoptosis. These results demonstrate the effectiveness of AA against NSCLC cells and that combinations of AA with 3-PO synergistically induce apoptosis via a ROS-dependent mechanism. These results support further evaluation of pharmacologic concentrations of AA as an adjuvant treatment for NSCLC and that combination of AA with glycolysis inhibitors may be a promising therapy for the treatment of NSCLC.

show abstract

“…Our previous study showed HA22T/VGH cells are susceptible to changes in redox status and oxidative stresses also induce apoptosis in these cells [20]. This study tested the effect of combining epirubicin with progesterone to treat a metastatic, poorly differentiated HCC cell line, HA22T/VGH.…”

Section: Introductionmentioning

confidence: 99%

Progesterone Increases Apoptosis and Inversely Decreases Autophagy in Human Hepatoma HA22T/VGH Cells Treated with Epirubicin

Cheng

Hsieh

Chiu

et al. 2014

The Scientific World Journal

Self Cite

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) is the leading cause of cancer-related deaths worldwide. Epirubicin can induce intracellular reactive oxygen species and is widely used to treat unresectable HCC. Progesterone has been found to inhibit the proliferation of hepatoma cells. This study was designed to test the combined effects of epirubicin and progesterone on human hepatoma cell line, HA22T/VGH. These cells were treated with different concentrations of epirubicin with or without the coaddition of 30 μM progesterone and then analyzed for apoptosis, autophagy, and expressions of apoptotic-related proteins and multidrug-resistant gene. Epirubicin treatment dose-dependently inhibited the growth of HA22T/VGH cells. Addition of 30 μM progesterone, which was inactive alone, augmented the effect of epirubicin on the inhibition of growth of HA22T/VGH cells. Cotreatment with progesterone enhanced epirubicin-induced apoptosis, as evidenced by greater increase in caspase-3 activity and in the ratio of the apoptosis-regulating protein, Bax/Bcl-XL. The combination also caused a decrease in autophagy and in the expression of multidrug resistance-related protein 1 mRNA compared to epirubicin alone. This study shows the epirubicin/progesterone combination was more effective in increasing apoptosis and inversely decreasing autophagy on HA22T/VGH cells treated with epirubicin alone, suggesting that this combination can potentially be used to treat HCC.

show abstract

Combined arginine and ascorbic acid treatment induces apoptosis in the hepatoma cell line HA22T/VGH and changes in redox status involving the pentose phosphate pathway and reactive oxygen and nitrogen species☆

Cited by 25 publications

References 42 publications

The pentose phosphate pathway: An antioxidant defense and a crossroad in tumor cell fate

The pentose phosphate pathway: An antioxidant defense and a crossroad in tumor cell fate

Ascorbic Acid and a Cytostatic Inhibitor of Glycolysis Synergistically Induce Apoptosis in Non-Small Cell Lung Cancer Cells

Progesterone Increases Apoptosis and Inversely Decreases Autophagy in Human Hepatoma HA22T/VGH Cells Treated with Epirubicin

Contact Info

Product

Resources

About