Tumor invasion is inhibited by phosphorylated ascorbate via enrichment of intracellular vitamin C and decreasing of oxidative stress

Nagao, Norio; Nakayama, Tomoko; Etoh, Tetsuya; Saiki, Ikuo; Miwa, Nobuhiko

doi:10.1007/s004320000120

Cited by 28 publications

(32 citation statements)

References 25 publications

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“…This is in accordance with previous research which showed that a derivative of AA, phospho-ascorbyl palmitate, had an antimetastatic effect on fibrosarcoma and melanoma cell lines by inhibiting the production and enzymatic activity of matrix metalloproteinases (MMP-2 and MMP-9) (34). It was also shown by Nagao et al that it takes repeated supplementation of L-ascorbic acid to inhibit tumor invasion by inhibiting the production of MMPs and cell motility (35), which would explain the high dose of AA required to induce an effect in our tested cell lines. While the mechanism behind MMP-2 expression is mostly unknown (36), the functional activity of MMPs is known to be detained by tissue inhibitors of metalloproteinases (TIMPs) and to be impacted by reactive oxygen species (roS), where excess production of roS, in association with the myeloperoxidase enzyme, would eventually inactivate MMPs (37).…”

Section: Discussionsupporting

confidence: 56%

“…In addition to its effects on HIV replication (29)(30)(31)(32)(33), and its anticancer effects (17), AA has shown inhibitory effects on matrix metalloproteinases (34,35). In our study, ascorbic acid was only effective against the MMP-2 gelatinolytic activity at the highest dose applied in each of the four malignant cell lines and this effect was independent of transcription and, at least in the case of the HTLV-1-negative cell lines, might be related to the AA inhibitory effect on translation.…”

Section: Discussionmentioning

confidence: 99%

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Effects of nutrients on matrix metalloproteinases in human T-lymphotropic virus type 1 positive and negative malignant T-lymphocytes

Harakeh

Khouzam

Damanhouri

et al. 2014

International Journal of Oncology

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Abstract.Experimental and clinical studies have revealed the effectiveness of a specific nutrient synergy (SNS) mixture composed of ascorbic acid (AA), lysine, proline, arginine, epigallocatechin gallate (EGCG) and other micronutrients in targeting crucial physiological mechanisms involved in cancer progression and metastasis. HTLV-1 causes adult T-cell leukemia (ATL). The spread and metastases of ATL as well as other tumors has been associated with matrix metalloproteinases, especially the gelatinases MMP-2 and MMP-9. The objective of this study was to investigate whether SNS, AA and EGCG affects the gelatinolytic activity of MMP-2 and its transcriptional and translational levels in HTLV-1-positive and -negative malignant T-cells. The results indicated that SNS and EGCG caused a dose-dependent decline in the activity, transcription and translation of MMP-2 after treatment with SNS and EGCG, while AA was only able to inhibit the activity at maximum doses tested and to some extent, the protein expression levels of MMP-2, without affecting their transcriptional levels. The highest activity was noted in the case of SNS which is likely to be due to a synergistic effect of the different constituents in the formulation. These results point towards the potential integration of SNS in the anti-invasive treatment of ATL and related diseases.

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Section: Discussionsupporting

confidence: 56%

Section: Discussionmentioning

confidence: 99%

Effects of nutrients on matrix metalloproteinases in human T-lymphotropic virus type 1 positive and negative malignant T-lymphocytes

Harakeh

Khouzam

Damanhouri

et al. 2014

International Journal of Oncology

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“…The latter peroxide may be a cause for spontaneous invasion of AH109A cells, because tumor cells are known to produce a large amount of ROS compared with normal cells (Szatrowski and Nathan 1991). Phosphorylated ascorbate is also reported to inhibit tumor invasion by decreasing oxidative stress (Nagao et al 2000). .…”

Section: Discussionmentioning

confidence: 99%

Inhibitory Effect of Ascorbic Acid on the Proliferation and Invasion of Hepatoma Cells in Culture

2005

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Effect of ascorbic acid (AsA) on the proliferation and invasion of rat ascites hepatoma AH109A cells was investigated by measuring [ 3 H]thymidine incorporation into acid-insoluble fraction of the cells and by co-culturing the hepatoma cells with rat mesentery-derived mesothelial cells, respectively. AsA suppressed the invasion of AH109A cells in a dose-dependent manner at concentrations of 62.5-500 lM, while it inhibited the proliferation of the cells at higher concentrations of 250 and 500 lM. Hepatoma cells previously cultured with hypoxanthine (HX) and xanthine oxidase (XO) or with hydrogen peroxide showed increased invasive activities. AsA suppressed the reactive oxygen species-potentiated invasive capacity by simultaneously treating AH109A cells with AsA, HX and XO or with AsA and hydrogen peroxide. Furthermore, AsA reduced the intracellular peroxide levels in AH109A cells. These results suggest that the antioxidative property of AsA may be involved in its anti-invasive action on hepatoma cells.

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“…60 In contrast, ROS are key participants in the progression cancer. Scavenging of ROS leads to diminished peritoneal tumor recurrence, 61 inhibits production of matrix metalloproteinase and cell motility 62 and inhibits degradation of the basement membrane. 63 Through these mechanisms, antioxidants might prevent tumor invasion or metastasis in prostate cancer cells.…”

Section: Effect Of Genistein On Antioxidant Enzymes Activities In Lncmentioning

confidence: 99%

Genistein, a soy isoflavone, induces glutathione peroxidase in the human prostate cancer cell lines LNCaP and PC‐3

Suzuki

Koike

Matsui

et al. 2002

Intl Journal of Cancer

170

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Genistein is a major component of soybean isoflavone and has multiple functions resulting in antitumor effects. Prostate cancer is 1 of the targets for the preventive role of genistein. We examined the effect of genistein on human prostate cancer (LNCaP and PC-3) cells. Proliferation of both cell lines was inhibited by genistein treatment in a dose-dependent manner. To obtain the gene expression profile of genistein in LNCaP cells, we performed cDNA microarray analysis. The expression of many genes, including apoptosis inhibitor (survivin), DNA topoisomerase II, cell division cycle 6 (CDC6) and mitogen-activated protein kinase 6 (MAPK 6), was downregulated. Expression levels were increased more than 2-fold in only 4 genes. The glutathione peroxidase (GPx)-1 gene expression level was the most upregulated. Quantitative real-time polymerase chain reaction revealed significant elevation of transcript levels of GPx-1 in both LNCaP and PC-3 cells. Upregulation of gene expression levels accompanied elevation of GPx enzyme activities. In contrast, no significant changes were observed in the gene expression levels and enzyme activities of the other antioxidant enzymes, superoxide dismutase and catalase. GPx activation might be one of the important characteristics of the effects of genistein on prostate cancer cells.

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Tumor invasion is inhibited by phosphorylated ascorbate via enrichment of intracellular vitamin C and decreasing of oxidative stress

Cited by 28 publications

References 25 publications

Effects of nutrients on matrix metalloproteinases in human T-lymphotropic virus type 1 positive and negative malignant T-lymphocytes

Effects of nutrients on matrix metalloproteinases in human T-lymphotropic virus type 1 positive and negative malignant T-lymphocytes

Inhibitory Effect of Ascorbic Acid on the Proliferation and Invasion of Hepatoma Cells in Culture

Genistein, a soy isoflavone, induces glutathione peroxidase in the human prostate cancer cell lines LNCaP and PC‐3

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