Synergistic Killing of Ehrlich Ascites Carcinoma Cells by Ascorbate and 3-Amino-1,2,4,-triazole

Benade, L.E.; Howard, Tanya M.; Burk, Dean

doi:10.1159/000224465

Cited by 118 publications

(56 citation statements)

References 4 publications

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“…The overall plausibility of ascorbic acid administered intravenously as a cancer therapy is enhanced by recent insights into clinical pharmacokinetics and in vitro cancer-specific cytotoxicity of vitamin C. [15][16][17][18][19][20] Pharmacokinetics data show that orally administered vitamin C results in tightly controlled plasma and cell concentrations. Subjects consuming 200-300 mg per day of vitamin C in 5 or more daily servings of fruits and vegetables have fasting steady state plasma concentrations of about 70-80 µmol/L.…”

Section: Discussionmentioning

confidence: 99%

“…Concentrations of 1000-5000 µmol/L are selectively cytotoxic to tumour cells in vitro, [16][17][18][19][20] and emerging evidence indicates that ascorbic acid at concentrations achieved only by the intravenous route may function as a pro-drug for hydrogen peroxide delivery to tissues. 20 The in vitro biologic evidence and clinical pharmacokinetics data confer biological plausibility to the notion that vitamin C could affect cancer biology and may explain in part the negative results of the Mayo Clinic trials.…”

Section: 10mentioning

confidence: 99%

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Intravenously administered vitamin C as cancer therapy: three cases

Padayatty

Riordan²,

Hewitt³

et al. 2006

Canadian Medical Association Journal

229

163

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Section: Discussionmentioning

confidence: 99%

Section: 10mentioning

confidence: 99%

Intravenously administered vitamin C as cancer therapy: three cases

Padayatty

Riordan²,

Hewitt³

et al. 2006

Canadian Medical Association Journal

229

163

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show abstract

“…Several mechanisms have been proposed by which vitamin C may be useful in treating cancer, including speculation that it improves immune response, reduces the severity of cachexia, and strengthens extracellular matrix against tumour cell invasion (Cameron et al, 1979;Henson et al, 1991). The ability of ascorbate to kill tumour cells preferentially through hydrogen peroxide generation has been confirmed in several in vitro studies (Bram et al, 1980;Leung et al, 1993) (Benade et al, 1969;Riordan et al, 1995). Rodent studies indicate that ascorbate supplementation can inhibit tumour growth in vivo (Tsao et al, 1988;Varga and Airoldi, 1983).…”

Section: Discussionmentioning

confidence: 99%

“…At sufficient concentrations, vitamin C can produce cytotoxic levels of hydrogen peroxide. Tumour cells are often catalase deficient and therefore more sensitive than normal to hydrogen peroxide (Benade et al, 1969). Vitamin C accumulates in solid tumours at concentrations higher than those in surrounding normal tissue (Langemann et al, 1989;Agus et al, 1999).…”

mentioning

confidence: 99%

Cytotoxicity of ascorbate, lipoic acid, and other antioxidants in hollow fibre in vitro tumours

Casciari¹,

Riordan²,

Schmidt³

et al. 2001

Br J Cancer

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Summary Vitamin C (ascorbate) is toxic to tumour cells, and has been suggested as an adjuvant cancer treatment. Our goal was to determine if ascorbate, in combination with other antioxidants, could kill cells in the SW620 hollow fibre in vitro solid tumour model at clinically achievable concentrations. Ascorbate anti-cancer efficacy, alone or in combination with lipoic acid, vitamin K 3 , phenyl ascorbate, or doxorubicin, was assessed using annexin V staining and standard survival assays. 2-day treatments with 10 mM ascorbate increased the percentage of apoptotic cells in SW620 hollow fibre tumours. Lipoic acid synergistically enhanced ascorbate cytotoxicity, reducing the 2-day LC 50 in hollow fibre tumours from 34 mM to 4 mM. Lipoic acid, unlike ascorbate, was equally effective against proliferating and nonproliferating cells. Ascorbate levels in human blood plasma were measured during and after intravenous ascorbate infusions. Infusions of 60 g produced peak plasma concentrations exceeding 20 mM with an area under the curve (24 h) of 76 mM h. Thus, tumoricidal concentrations may be achievable in vivo. Ascorbate efficacy was enhanced in an additive fashion by phenyl ascorbate or vitamin K 3 . The effect of ascorbate on doxorubicin efficacy was concentration dependent; low doses were protective while high doses increased cell killing.

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“…VC exhibits selective toxicity toward melanoma (Bram et al, 1980), leukemia (Park et al, 1980), neuroblastoma (Prasad et al, 1979b), and ascite (Liotti et al, 1984) cell lines by inhibiting cancer cell growth in vitro (Benade et al, 1969;Yamafuji et al, 1971;Koch and Biaglow, 1978;De Loecker et al, 1993;Leung et al, 1993;Medina et al, 1994;Gilloteaux et al, 1995Gilloteaux et al, , 1998aGilloteaux et al, , 1998bGilloteaux et al, , 2001aGilloteaux et al, , 2001bGilloteaux et al, , 2001cGilloteaux et al, , 2003aGilloteaux et al, , 2003bGilloteaux et al, , 2004Gilloteaux et al, , 2005Jamison et al, 1996Jamison et al, , 2002Jamison et al, , 2004Jamison et al, , 2005Menon et al, 1998). VC is selectively toxic to tumor cells in vivo (Pierson and Meadows, 1983;Varga and Airoldi, 1983;Tsao et al, 1988;Taper et al, 2001) and can kill cells in solid primary tumors and metastases (Taper et al, 1987(Taper et al, , 1996Taper and Roberfroid, 1992).…”

Section: Cytotoxicity Of Ascorbatementioning

confidence: 99%

Morphology and DNA degeneration during autoschizic cell death in bladder carcinoma T24 cells induced by ascorbate and menadione treatment

Gilloteaux¹,

Jamison²,

Arnold³

et al. 2005

Anat. Rec.

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Feulgen and actin-phalloidin staining as well as gel electrophoresis have been employed in conjunction with cell ultrastructure to describe the effects of 1-, 2-, and 4-hr ascorbate (VC), menadione (VK 3 ), and ascorbate:menadione (VC:VK 3 ) treatments on the T24 human bladder carcinoma cell line. T24 cells exposed to VC alone display blebs and other superficial membrane defects related to membrane alterations and to superficial cytoskeleton changes. VK 3 treatment damages the cell nucleus and organelles, leads to the redistribution of the organelles in the perikaryon as a consequence of cytoskeletal damage, and results in cytoplasmic self-excisions. After VC:VK 3 treatment, the cells show exaggerated alterations characteristic of each vitamin treatment alone, including damaged mitochondria, self-excision of organelle-free pieces of cytoplasm, and extrusion of the perikaryon containing a nucleus surrounded by the damaged organelles. The nuclear envelope appears intact and contains chromatin that decondenses and dissipates. During the cellular demise that concludes with apparent karyolysis, the cells significantly decrease their size and alter their shape. However, the cisterns of rough endoplasmic reticulum are undamaged, but may become dilated. Since the cellular phenomena leading to cell death differ morphologically from apoptosis and necrosis, but entail selfcutting without nuclear bodies, this new form of cell death was called autoschizis. In addition, gel electrophoresis and Feulgen staining demonstrate that autoschizis is accompanied by random DNA degeneration.

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Synergistic Killing of Ehrlich Ascites Carcinoma Cells by Ascorbate and 3-Amino-1,2,4,-triazole

Cited by 118 publications

References 4 publications

Intravenously administered vitamin C as cancer therapy: three cases

Intravenously administered vitamin C as cancer therapy: three cases

Cytotoxicity of ascorbate, lipoic acid, and other antioxidants in hollow fibre in vitro tumours

Morphology and DNA degeneration during autoschizic cell death in bladder carcinoma T24 cells induced by ascorbate and menadione treatment

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