Effect of Arginine on Growth of Squamous Cell Carcinoma in the C3H/KM Mouse

Hester, Jerome E.; Fee, Willard E.

doi:10.1001/archotol.1995.01890020055011

Cited by 6 publications

(3 citation statements)

References 15 publications

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“…Some oncologists have recommended Arg supplementation to enhance cell-kill rate during chemotherapy (Brittenden et al, 1994), supposedly through boosting host immunosurveillance mechanisms (Hester and Fee, 1995). The case is not proven, and therefore more consideration ought perhaps be given to arginine deprivation, which has had a following in the past (Wheatley, 1998).…”

Section: Implications Of Selective Tumour Cell Destruction For Cancermentioning

confidence: 99%

Single amino acid (arginine) deprivation: rapid and selective death of cultured transformed and malignant cells

et al. 2000

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The effects of arginine deprivation (–Arg) has been examined in 26 cell lines. Less than 10% of those with transformed or malignant phenotype survived for > 5 days, and many died more rapidly, notably leukaemic cells. Bivariate flow cytometry confirmed that vulnerable cell lines failed to move out of cell cycle into a quiescent state (G0), but reinitiated DNA synthesis. Many cells remained in S-phase, and/or had difficulty progressing through to G2 and M. Two tumour lines proved relatively ‘resistant’, A549 and MCF7. Although considerable cell loss occurred initially, both lines showed a ‘cell cycle freeze’, in which cells survived for > 10 days. These cells recovered their proliferative activity in +Arg medium, but behaved in the same manner to a second –Arg episode as they did to the first episode. In contrast, normal cells entered G0 and survived in –Arg medium for several weeks, with the majority of cells recovering with predictable kinetics in +Arg medium. In general, cells from a wide range of tumours and established lines die quickly in vitro following –Arg treatment, because of defective cell cycle checkpoint stringency, the efficacy of the treatment being most clearly demonstrated in co-cultures in which only the normal cells survived. The findings demonstrate a potentially simple, effective and non-genotoxic strategy for the treatment of a wide range of cancers. © 2000 Cancer Research Campaign

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Section: Implications Of Selective Tumour Cell Destruction For Cancermentioning

confidence: 99%

Single amino acid (arginine) deprivation: rapid and selective death of cultured transformed and malignant cells

et al. 2000

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“…In addition to the mechanisms of action suggested, arginine is a precursor of nitric oxide (NO), whose pharmacological actions have been related to the inhibition of tumor cell growth in vitro [5,14,18], cytology of the activated macrophages, and inhibition of neotrophil aggregation [5] besides participating in various physiological and pathophysiological phenomena, including blood pressure regulation, neurotransmission and cell-mediated immunity [16].…”

Section: Growth Of the Walker 256 Tumormentioning

confidence: 99%

Metabolic and Hematological Effects of Dietary Supplementation with Arginine on Rats Bearing Ascitic Walker 256 Tumor

Novaes

Lima²,

Novaes³

et al. 2004

Ann Nutr Metab

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The notion of using supplementary quantities of arginine for nutritional support in patients with cancer has been evaluated not only as supplement intake of nitrogen substrate but also for its immunopharmacological effects capable of improving the patient‘s prognosis. The aim of the present study is to evaluate the effects of dietary supplementation with arginine on metastatic dissemination, amino acid metabolism, hematological functions of rats with Walker 256 ascitic tumor. Animals were inoculated intraperitoneally with approximately 4 million cells. Nutritional solutions containing 4 or 6% arginine or just a control diet without added arginine, were administered to the animals via esophagic gavages. The rate of metastasis was lower in animals supplemented with arginine at 4 and 6%. Amino acid metabolism was stimulated in tumor-bearing animals after receiving 4 or 6% arginine, demonstrated by significant increase of arginine, ornithine, citrulline, proline and histidine levels in the blood (p ≤ 0.001) when compared to the control diet group. Anemia was less severe in tumor-bearing animals that received arginine supplementation. The findings suggest that arginine supplementation at 6% may have a beneficial effect on to the host, besides its pharmacological action.

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“…Ogilvie et al [14] found that excess Arg combined with doxorubicin chemotherapy extended disease-free interval and survival time of dogs with lymphoma. According to the studies of Hester and Fee [15] on squamous cell carcinoma in the CH3/KM mouse the mechanism of action of high amounts of Arg may be the stimulation of host immune surveillance. However, Robinson et al [16] found that Morris hepatoma-bearing rats fed with Arg-rich diet did not show any alteration in tumour growth or cytokine production.…”

Section: Effect Of Arg Deprivation and Supplementation On Tumour Cellmentioning

confidence: 99%

Role of arginine and its methylated derivatives in cancer biology and treatment

2001

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Both L-arginine supplementation and deprivation influence cell proliferation. The effect of high doses on tumours is determined by the optical configuration: L-arginine is stimulatory, D-arginine inhibitory. Arginine-rich hexapeptides inhibited tumour growth. Deprivation of L-arginine from cell cultures enhanced apoptosis. The pro-apoptotic action of NO synthase inhibitors, like NGmonomethyl-L-arginine, is manifested through inhibition of the arginase pathway. NGhydroxymethyl-L-arginines caused apoptosis in cell cultures and inhibited the growth of various transplantable mouse tumours. These diverse biological activities become manifest through formaldehyde (HCHO) because guanidine group of L-arginine in free and bound form can react rapidly with endogenous HCHO, forming NG-hydroxymethylated derivatives. L-arginine is a HCHO capturer, carrier and donor molecule in biological systems. The role of formaldehyde generated during metabolism of NG-methylated and hydroxymethylated arginines in cell proliferation and death can be shown. The supposedly anti-apoptotic homozygous Arg 72-p53 genotype may increase susceptibility of some cancers. The diverse biological effects of L-arginine and its methylated derivatives call for further careful studies on their possible application in chemoprevention and cancer therapy.

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Effect of Arginine on Growth of Squamous Cell Carcinoma in the C3H/KM Mouse

Cited by 6 publications

References 15 publications

Single amino acid (arginine) deprivation: rapid and selective death of cultured transformed and malignant cells

Single amino acid (arginine) deprivation: rapid and selective death of cultured transformed and malignant cells

Metabolic and Hematological Effects of Dietary Supplementation with Arginine on Rats Bearing Ascitic Walker 256 Tumor

Role of arginine and its methylated derivatives in cancer biology and treatment

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