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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☆ by Bau-Shan Hsieh; Li-Wen Huang; Shu-Jem Su; Hsiao-Ling Cheng; Yu-Chen Hu; Thu-Ching Hung; Kee-Lung Chang is a Medicine article available to read on EtoBox.

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Arginine is a physiological substrate for nitric oxide synthase to generate nitric oxide (NO), which can influence tumor cell survival, while ascorbic acid is selectively toxic for cancer cells. This study explored the effect of an arginine/ascorbic acid combination on human cancer cell lines. The hepatoma cell line HA22T/VGH was the most sensitive of the tested cells to combination treatment. A combination of 5.74 mM of arginine and 0.57 mM of ascorbic acid induced HA22T/VGH cell death through apoptosis and an increase in levels of reactive oxygen species and NO, as well as its stable products NO 2 -and NO 3 -. The combination also reduced the activity of glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and transaldolase in the pentose phosphate pathway, a major mechanism for producing NADPH, resulting in a marked decrease in intracellular NADPH levels. A dramatic decrease in intracellular glutathione (GSH) levels, a decrease in the mitochondrial membrane potential, ATP depletion and release of cytochrome c were also seen. Caspase-9 and caspase-3 were activated, apoptotic protein Bax expression increased and the expression of the anti-apoptotic proteins Bcl-2 a

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Author

Bau-Shan Hsieh; Li-Wen Huang; Shu-Jem Su; Hsiao-Ling Cheng; Yu-Chen Hu; Thu-Ching Hung; Kee-Lung Chang

Publisher

Elsevier Science; Elsevier ; Elsevier BV (ISSN 0955-2863)

Published

2011

Language

EN

Field

Medicine (Health Sciences)