Orthomolecular Oncology Review: Ascorbic Acid and Cancer 25 Years Later

González, Michael J.; Miranda-Massari, Jorge R.; Mora, Edna; Guzmán, Angelik; Riordan, Neil H; Riordan, Hugh D.; Casciari, Joseph J.; Jackson, James; Román-Franco, Ángel A.

doi:10.1177/1534735404273861

Cited by 113 publications

(107 citation statements)

References 110 publications

(163 reference statements)

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“…Intracellular ascorbate concentrations in the low millimolar range (much higher than that in plasma) seem to be necessary to support its role as an antioxidant [32] and as a cofactor for dioxygenase enzymes [33]. Whether vitamin C functions as an antioxidant or pro-oxidant is determined by at least three factors: 1) the redox-potential of the cellular environment; 2) the presence/absence of transition metals; and 3) the local concentrations of ascorbate [34][35][36]. The last factor is particularly relevant in treatments that depend on the antioxidant/ pro-oxidant property of vitamin C, because it can be readily manipulated and controlled in vivo to achieve desired effects [34].…”

Section: Vitamin C As An Antioxidantmentioning

confidence: 99%

An Overview of the Characteristics and Function of Vitamin C in Various Tissues: Relying on its Antioxidant Function

Akbari

Jelodar

Nazifi

et al. 2016

Zahedan J Res Med Sci

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Vitamin C (L-ascorbic acid or ascorbate) is a biomolecule that participates in many biochemical processes. It is an essential nutrient for humans, however, in some species such as rodents and guinea pigs is synthesized. It has a variety of functions in the body that we might venture to say make it a very important antioxidant nature and pro-oxidant. L-ascorbic acidic a reduced form of vitamin C and dehydroascorbic acid (DHA) is the oxidized form of ascorbate, both L-ascorbic acid and dihydroascorbic acid retain the vitamin C activity. Dehydro-ascorbate is reconverted to ascorbate in the cytosol by cytochrome b reductase and thioredoxin reductase in reactions involving NADH and NADPH, respectively. Ascorbate is transported into the cell via the sodium-dependent vitamin C transporters (SVCTs), which causes accumulation of ascorbate within cells against a concentration gradient. Dehydroascorbic acid, the oxidized form of ascorbate, is transported via glucose transporters family (GLUTs). The highest concentrations of ascorbate in the body are found in brain and adrenal gland. Vitamin C also acts as a co-factor in several enzyme reactions. This vitamin is an essential biochemical factor in the reproductive process. The pharmacophore of vitamin C is the ascorbate, ascorbate is an antioxidant.Ascorbate is a neuromodulator of glutamatergic and dopaminergic system and related behaviors. It also improves components of the immune system. Given the wide role of ascorbate, further investigation is necessary to evaluate the exact mechanism(s) underlying these effects. In this review we will consider a short overview of the characteristics and function of vitamin C (relying on antioxidant function) in various tissues.

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Section: Vitamin C As An Antioxidantmentioning

confidence: 99%

An Overview of the Characteristics and Function of Vitamin C in Various Tissues: Relying on its Antioxidant Function

Akbari

Jelodar

Nazifi

et al. 2016

Zahedan J Res Med Sci

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“…An antioxidative property may be defined as a capacity for the scavenging of free radicals including ROS and reactive nitrogen species by donating a hydrogen or an electron (35). There have been many reports of the therapeutic or preventive efficacy of vitamin C as an anticancer agent (36,37), but no study of the DENinduced HCC model has been conducted using congenital vitamin C-deficient Smp30 KO mice. In the present study, we promote the proliferation of surviving hepatocytes as a compensatory effect (39).…”

Section: Discussionmentioning

confidence: 99%

Preventive Effects of Vitamin C on Diethylnitrosamine-induced Hepatotoxicity in Smp30 Knockout Mice

Son

Ullah

Elfadl

et al. 2018

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Abstract. Vitamin C (L-ascorbic Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death, resulting in approximately 0.7 million deaths each year, and the sixth most common malignancy worldwide (1-3). The recognized risk factors for HCC are hepatic disorder associated with steatosis, cirrhosis, viral hepatitis, alcohol, chemical agents, obesity, metabolic syndrome, and so forth (4). Despite recent advances in diagnosis and treatment, the effectiveness of therapy for HCC remains unsatisfactory, and HCC has a hidden development and a poor prognosis (5, 6). Therefore, there is an urgent requirement for novel therapeutic compounds for the treatment of patients with HCC. Many animal models of hepatocarcinogenesis have been established to examine the effects of therapeutic agents. Diethylnitrosamine (DEN) is frequently used as a hepatocarcinogenic agent in rodents (1). In our experimental model, externally visible foci were observed and measured by stereomicroscopy. It has been established that DEN induces HCC in animals with a developmental course similar to that of human HCC (7). Furthermore, DEN is an indirect alkylating agent that induces the generation of reactive oxygen species (ROS), which damage DNA through oxidation (8).Senescence marker protein-30 (SMP30) is a calciumbinding protein, and its levels in the liver, kidney, and lung become significantly down-regulated with aging in an androgen-independent manner (9, 10). SMP30 plays an important role in calcium (Ca 2+ ) homeostasis (11). Ca 2+ is one of the most universal and physiologically significant signaling molecules that especially affects cell apoptosis and cell necrosis (12). Other reports have indicated that SMP30 participates in controlling the activity of antioxidant enzymes 93

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“…Vitamin C has previously been used as an unorthodox therapy for patients with cancer (14); however, in most clinical settings, vitamin C is used as an auxillary treatment and the dosage is low. Low-dose vitamin C (25-50 µg/ml) does not induce apoptosis; conversely, it is associated with stem cell proliferation and maintenance (4,8).…”

Section: Discussionmentioning

confidence: 99%

In vitro and in vivo assessment of high-dose vitamin C against murine tumors

Wang

Yin

Wang

2016

Experimental and Therapeutic Medicine

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Abstract. Vitamin C is widely used in clinical settings and is well known for its safety. Previous studies have shown the efficacy of intravenous vitamin C; however, intratumoral delivery of vitamin C has yet to be attempted. In the present study, the biological effects of high-dose vitamin C on tumor cells were investigated in vitro by using the MTT assay and flow cytometry. When administered in vitro, high-dose vitamin C inhibited the proliferation of murine colon and breast cancer cells, and induced tumor cell apoptosis. Cytotoxicity of vitamin C was partially reversed by N-acetyl-cysteine at a relatively low dosage. In addition, synergistic anti-tumor effects of vitamin C and cisplatin were observed. In vivo, intratumoral delivery of vitamin C delayed tumor growth in murine solid tumor models. Considering its low toxicity and availability, the present study indicates that vitamin C may be a novel therapeutic method for patients with advanced tumors.

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Orthomolecular Oncology Review: Ascorbic Acid and Cancer 25 Years Later

Cited by 113 publications

References 110 publications

An Overview of the Characteristics and Function of Vitamin C in Various Tissues: Relying on its Antioxidant Function

An Overview of the Characteristics and Function of Vitamin C in Various Tissues: Relying on its Antioxidant Function

Preventive Effects of Vitamin C on Diethylnitrosamine-induced Hepatotoxicity in Smp30 Knockout Mice

In vitro and in vivo assessment of high-dose vitamin C against murine tumors

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