Depletion of Dietary Arginine Inhibits Growth of Metastatic Tumor

Yeatman, Timothy J.; Risley, Geoffrey L.; Brunson, Mathew E.

doi:10.1001/archsurg.1991.01410350066010

Cited by 68 publications

(45 citation statements)

References 9 publications

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“…For example, Gilroy in 1930 15 and Yeatman et al in 1991 16 demonstrated that mice fed an arginine-enriched diet developed tumors that grew faster and larger than mice fed a normal diet. Conversely, mice fed an arginine-deficient diet have reduced tumor growth.…”

Section: Discussionmentioning

confidence: 99%

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Incidence and distribution of argininosuccinate synthetase deficiency in human cancers

Dillon

Prieto

Curley

et al. 2004

Cancer

270

229

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BACKGROUND Argininosuccinate synthetase (ASS) was the first of two enzymes to convert citrulline to arginine. This pathway allowed cells to synthesize arginine from citrulline, making this amino acid nonessential for the growth of most mammalian cells. Previous studies demonstrated that several human tumor cell lines were auxotrophic for arginine due to an inability to express ASS. Selective elimination of arginine from the circulation of animals with these tumors is a potentially effective anticancer treatment. The purpose of these experiments was to determine the frequency of ASS deficiency and arginine auxotrophy in a variety of human malignant tumors. METHODS The authors analyzed the expression of ASS by immunohistochemistry with a monoclonal antibody in a variety of human tumor biopsies. They found that the incidence of ASS deficiency varied greatly with the tumor type and tissue of origin. RESULTS Melanoma, hepatocellular carcinoma, and prostate carcinoma were most frequently deficient in ASS. Some human cancers were almost always positive for ASS (e.g., lung and colon carcinomas). However, other human cancers, including sarcomas, invasive breast carcinoma, and renal cell carcinoma, also were sometimes ASS deficient. CONCLUSIONS These data indicated that immunohistochemical detection of ASS may prove an effective means for determining ASS deficiency in malignant human tumors and for identifying patients most likely to respond to arginine deprivation therapy. Based on these results, human clinical trials using arginine‐degrading enzyme therapy to treat patients with advanced melanoma or hepatocellular carcinoma have been initiated. Cancer 2004;100:826–33. © 2004 American Cancer Society.

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Section: Discussionmentioning

confidence: 99%

“…Conversely, mice fed an arginine-deficient diet have reduced tumor growth. 16,17 Therefore, there is a long history of evidence in the nutritional literature indicating a requirement for arginine in the growth of some tumors.…”

Section: Discussionmentioning

confidence: 99%

Incidence and distribution of argininosuccinate synthetase deficiency in human cancers

Dillon

Prieto

Curley

et al. 2004

Cancer

270

229

View full text Add to dashboard Cite

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“…Many of these biologic products have been implicated in tumor development, and therefore, feeding mice with arginine enhances tumor growth (5). In contrast, depletion of dietary arginine inhibits liver metastasis (6).…”

Section: Introductionmentioning

confidence: 99%

Attenuation of Argininosuccinate Lyase Inhibits Cancer Growth via Cyclin A2 and Nitric Oxide

Huang

Hsu

Shieh

et al. 2013

Molecular Cancer Therapeutics

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Arginine biosynthesis and nitric oxide (NO) production are important for cancer homeostasis. Degradation of arginine may be used to inhibit liver tumors with low argininosuccinate synthetase (ASS) expression. In this report, we investigated an alternative therapeutic approach by targeting argininosuccinate lyase (ASL). ASL is transcriptionally induced by endoplasmic reticulum stress and is overexpressed in some human liver tumors. Knockdown of ASL expression by short hairpin RNA (shRNA) in three liver cancer cell lines, ML-1, HuH-7, and HepG2, decreased colony formation in vitro and tumor growth in vivo. Furthermore, lentiviral infection of ASL shRNA inhibited tumor growth in a therapeutic animal tumor model. Analysis of ASL shRNA on the cellcycle progression revealed a G 2 -M delay. Among cell-cycle regulatory molecules, cyclin A2 expression was reduced. Reintroduction of exogenous cyclin A2 restored the cell growth in ASL-knockdown cells. Autophagy was observed in the cells treated with ASL shRNA, as shown by an increase in LC3-II levels and autophagosome formation. The total cellular arginine level was not altered significantly. Inhibition of autophagy further attenuated cell growth, suggesting that autophagy induced by ASL shRNA plays a feedback prosurvival function. Knockdown of ASL reduced NO content, and addition of NO donor partially recovered the growth inhibition by ASL shRNA. In summary, downregulation of ASL attenuated tumor growth and the inhibition was mainly mediated by a decrease of cyclin A2 and NO.

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“…Such factors include beta fibroblast proliferation-stimulating GF (FGFb), platelet-derived growth factor (PDGF), hepatocyte growth factor (HGF), and others (4)(5)(6). It is important therefore to design combined treatments that will inhibit residual tumor cell proliferation following surgery, without impairment of the healing process.…”

Section: Introductionmentioning

confidence: 99%

Effects of all-trans retinoic acid on tumor recurrence and metastasis

Garcı́a-Alonso

Palomares

Portugal

et al. 2005

Rev. esp. enferm. dig.

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Objective: all-trans-retinoic acid (ATRA) promotes cell differentiation. We have studied its effect on the local recurrence and metastatic spreading of an experimental rhabdomyosarcoma in rats.Design: syngenic rhabdomyosarcoma cells (S4MH) were inoculated s.c. in male WAG/RijCrl rats. After 25 days tumors were excised and a 40% hepatectomy was performed for all animals. Ten days later the rats were sacrificed and a thorough necropsy was performed. The animals were randomly allocated to receive daily doses of ATRA (5 mg/kg, i.p.) or its solvent (Clinoleic ® /ethanol 90/10), starting three days before surgery until the end of the experiment.Results: ATRA reduced the incidence of local recurrence from 70 to 33% (p < 0.05), but the tumor size was not altered (1.8 vs. 2.0 cc). Regarding inguinal metastasis, there was a sixfold decrease (0.2 vs. 1.2 cc; p < 0.05) in mean tumor volume, although the rate of this proliferation increased sharply (86 vs. 29%; p < 0.05) for treated animals. The volume of the retroperitoneal tumor masses also decreased with ATRA (0.7 vs. 5.1 cc; p < 0.05), but the difference in rate was not significant (71 vs. 67%). Lung metastases, which were present in 100% of control animals, were found in only 33% of treated rats, while the mean number of metastatic foci dropped from 26.7 to 5.7 (p < 0.05).Conclusion: protocols including retinoid administration prior to and following primary tumor excision could help in controlling both recurrence and metastatic progression in surgically treated rhabdomyosarcoma.Key words: Rat. Rhabdomyosarcoma. Recurrence. Metastasis. All-trans-retinoic acid. García-Alonso I, Palomares T, Alonso INTRODUCTIONOver the past decade, remarkable progress has been made in antineoplastic therapy, with surgery still in the forefront as the main curative approach. However, recurrence of disease following tumor resection remains a major problem, not only because of failed local control but also because of the effect of surgery on the distant proliferation of disease, thus reducing patient quality of life and survival (1).While tumor recurrence depends to a great extent on the radicality of surgery, it can also be induced by biological responses initiated following tissue aggression as implied by the operation itself. Indeed, in an experimental carcinogenesis model, researchers observed that the rate of colon tumor development following a carcinogen was much higher within healing anastomoses in the colon (2).Surgery, it must be remembered, triggers local release of multiple growth factors (GF) that are responsible for wound healing, but which may also act as paracrine factors giving tumor cells the signal they require to divide and proliferate (3). Such factors include beta fibroblast proliferation-stimulating GF (FGFb), platelet-derived growth factor (PDGF), hepatocyte growth factor (HGF), and others (4-6). It is important therefore to design combined treatments that will inhibit residual tumor cell proliferation following surgery, without impairment of the healing process.Today ...

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Depletion of Dietary Arginine Inhibits Growth of Metastatic Tumor

Cited by 68 publications

References 9 publications

Incidence and distribution of argininosuccinate synthetase deficiency in human cancers

Incidence and distribution of argininosuccinate synthetase deficiency in human cancers

Attenuation of Argininosuccinate Lyase Inhibits Cancer Growth via Cyclin A2 and Nitric Oxide

Effects of all-trans retinoic acid on tumor recurrence and metastasis

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