Inhibition of gastric cancer cell growth by arginine: Molecular mechanisms of action

Nanthakumaran, Shayanthan; Brown, Iain; Heys, Steven Darryll; Schofield, Andrew Craig

doi:10.1016/j.clnu.2008.10.007

Cited by 22 publications

(17 citation statements)

References 24 publications

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“…The ability of Arg to inhibit the tumor growth based on the metabolism of Arg or based on its chemical structure has been verified and confirmed. Arg when incubated in medium for 24-72 h had been shown to kill gastric cancer cells through apoptosis based on the metabolism of Arg [7,8]. Yurtcu et al [4] have reported also that based on the metabolism Arg could induce DNA damage with rising of NO in lymphocytes.…”

Section: Introductionmentioning

confidence: 99%

Administering the Optimum Dose of l-Arginine in Regional Tumor Therapy

Moawad

2013

Ind J Clin Biochem

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The purpose of this study is optimizing the Larginine (L-Arg) doses on the basis of chemical structure in regional accessible tumor therapy to settle down a new protocol for the treatment of cancer.3 H-thymidine-based cell proliferation assay was performed in vitro on tumor cell lines of fibrosarcoma (FS), lymphosarcoma-ascitic and on normal cell line of NIH 3T3 after treatment with different concentrations of L-Arg in phosphate buffered saline (PBS). The cultures were harvested after 22 h and the incorporated radioactivity was counted to identify their histologic grades as described in earlier studies. In vivo therapy of murine tumors was conducted where FS cells injected subcutaneously at ventro-lateral position of mice. Various drug delivery schedules were injected into the centre of tumor base, once a day for 4 days. Tumor diameter and survivals were monitored where the day of sacrifice was considered for monitoring the survival period. By identifying the histologic grades of the treated cultures in vitro and in vivo by different concentrations of L-Arg, the corresponding energy of such concentrations were determined. An efficient model with a good fit (R 2 = 0.98) was established to describe the energy yield by L-Arg dose. The equivalence between the tumor histologic grade and energy of the L-Arg dose delivered in saline (PBS) environment is the optimum condition for regional tumor therapy achieves higher survival rate. The selective cytotoxicity to tumor cells with minimal damage to normal cells by L-Arg due to its chemical structure suggests to be considered the most promising drug for regional therapy of the accessible tumors like breast cancers of early stage with no distant metastasis.

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Section: Introductionmentioning

confidence: 99%

Administering the Optimum Dose of l-Arginine in Regional Tumor Therapy

Moawad

2013

Ind J Clin Biochem

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“…Arg when incubated in medium for 24-72 h had been shown to kill gastric cancer cells through apoptosis [6,7]. All the earlier studies suggested the ability of Arg to modify the tumor growth based on the metabolism of Arg [1-4, 6, 7].…”

Section: Discussionmentioning

confidence: 99%

“…However, L-Arg-M up to 50 mM stimulated the growth of tumor cells. Arg has been demonstrated to either inhibit or facilitate the growth through its metabolism [6,7]. Since the role of polyamines in cell growth, proliferation are demonstrated, Arg via arginase pathway could contribute to the enhanced tumor growth [1,4,5].…”

Section: Discussionmentioning

confidence: 99%

“…CRA was performed with tumor cell line LSA. Briefly, tumor cells (18X10 6 Tumor cell proliferation was measured according to the method described earlier [21]. …”

Section: Chromium Release Assay (Cra)mentioning

confidence: 99%

“…Arg and its metabolic products have been demonstrated to modulate immune, inflammatory and metabolic pathways and facilitate or inhibit the growth of the tumor [4][5][6][7]. Arg containing anticancer peptides (ACPs) have also been known to kill tumor cells by disrupting the cell membrane, through a non-metabolic process based on their structure.…”

Section: Introductionmentioning

confidence: 99%

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Arginine: Appropriate Dose and Delivery Environment Makes It an Anticancer Molecule~!2009-11-16~!2009-04-15~!2010-05-05~!

Shukla¹,

Thakur²,

Poduval³

2010

TOCJ

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Abstract:The electrostatic attraction between the negatively charged components of cancer cells and the positively charged anticancer peptides (ACPs) is believed to play a role in selective disruption of cancer cell membrane. Since arginine (Arg), a cationic amino acid is the most prevalent in these ACPs; we hypothesized that Arg when delivered in saline environment at the pharmacological concentration could become an anticancer molecule. The effects of L-Arg and D-Arg on tumor cell lines were studied. The therapeutic ability of pharmacological doses of Arg in saving the mice from experimental tumors was also evaluated. Both the enantiomers of Arg and not the cationic amino acid L-lysine (L-Lys) or agmatine-sulphate, at 10 mM concentration caused tumor cell clumping when treated in PBS. Arg delivered in PBS (Arg-P) and not in medium (Arg-M) up to 50 mM caused extensive tumor cell membrane damage leading to its death. Arg at 150 mM and above irrespective of chirality and incubation vehicle became an effective antitumor molecule against all the four cell lines tested. L-Arg was not toxic to normal cells like erythrocytes, lymphocytes, NIH 3T3 cells when presented in PBS. Arg cured mice bearing solid tumor fibrosarcoma (FS) when delivered into the tumor either in PBS or medium and lymphosarcoma-ascitic (LSA) tumor when delivered intraperitoneally in PBS. Our studies indicate that Arg can be used for loco-regional tumor therapy with minimal damage to normal cells and the mechanism of anticancer action of Arg is not metabolically driven but through its chemical structure, dose and delivery environment.

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Perioperative Immunonutrition in Major Abdominal Surgery

Cerantola¹,

Sch€afer²

2015

Diet and Nutrition in Critical Care

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Inhibition of gastric cancer cell growth by arginine: Molecular mechanisms of action

Cited by 22 publications

References 24 publications

Administering the Optimum Dose of l-Arginine in Regional Tumor Therapy

Administering the Optimum Dose of l-Arginine in Regional Tumor Therapy

Arginine: Appropriate Dose and Delivery Environment Makes It an Anticancer Molecule~!2009-11-16~!2009-04-15~!2010-05-05~!

Perioperative Immunonutrition in Major Abdominal Surgery

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