Arginine deiminase: a potential inhibitor of angiogenesis and tumour growth

Is, Park; Kang, Shin Wook; Shin, Young-jeon; Ky, Chae; Mo, Park; My, Kim; Dn, Wheatley; Bh, Min

doi:10.1038/sj.bjc.6601181

Cited by 75 publications

(52 citation statements)

References 33 publications

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“…Park et al also used HUVECs and recombinant ADI to show that ADI could inhibit angiogenesis in a dose dependent manner, and this inhibitory effect can be reversed by supplying arginine back to the culture medium [43]. Park et al also observed that recombinant ADI exerted inhibition of angiogenesis in their in vivo studies using chick embryo and mouse model [43]. This antiangiogenetic property of ADI suggested an effective way for treating tumors.…”

Section: Adi-peg20 Inhibits Angiogenesismentioning

confidence: 99%

“…Beloussow et al first [42] demonstrated the anti-angiogenic effect of recombinant ADI with cultured human umbilical vein endothelial cells (HUVEC). Park et al also used HUVECs and recombinant ADI to show that ADI could inhibit angiogenesis in a dose dependent manner, and this inhibitory effect can be reversed by supplying arginine back to the culture medium [43]. Park et al also observed that recombinant ADI exerted inhibition of angiogenesis in their in vivo studies using chick embryo and mouse model [43].…”

Section: Adi-peg20 Inhibits Angiogenesismentioning

confidence: 99%

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Arginine Deprivation as a Targeted Therapy for Cancer

Feun

You

et al. 2008

CPD

196

188

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Certain cancers may be auxotrophic for a particular amino acid and amino acid deprivation is one method to treat these tumors. Arginine deprivation is a novel approach to target tumors which lack argininosuccinate synthetase (ASS) expression. ASS is a key enzyme which converts citrulline to arginine. Tumors which usually do not express ASS include melanoma, hepatocellular carcinoma, some mesotheliomas and some renal cell cancers. Arginine can be degraded by several enzymes including arginine deiminase (ADI). Although ADI is a microbial enzyme from mycoplasma, it has high affinity to arginine and catalyzes arginine to citrulline and ammonia. Citrulline can be recycled back to arginine in normal cells which express ASS, whereas ASS(−) tumor cells cannot. A pegylated form of ADI (ADI-PEG20) has been formulated and has shown in vitro and in vivo activity against melanoma and hepatocellular carcinoma. ADI-PEG20 induces apoptosis in melanoma cell lines. However, arginine deprivation can also induce ASS expression in certain melanoma cell lines which can lead to in-vitro drug resistance. Phase I and II clinical trials with ADI-PEG20 have been conducted in patients with melanoma and hepatocellular carcinoma and antitumor activity has been demonstrated in both cancers. This article reviews our laboratory and clinical experience as well as others with ADI-PEG20 as an antineoplastic agent. Future direction in utilizing this agent is also discussed.

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Section: Adi-peg20 Inhibits Angiogenesismentioning

confidence: 99%

Section: Adi-peg20 Inhibits Angiogenesismentioning

confidence: 99%

Arginine Deprivation as a Targeted Therapy for Cancer

Feun

You

et al. 2008

CPD

196

188

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“…В частности, установлено, что АД подавляет пролиферацию трансформированных клеток и оказывает противоопухолевое действие in vivo с минимальными побочными эффекта-ми [12,15]. Предполагают, что подавление роста опухолевых клеток происходит благодаря амино-кислотному голоданию из-за деплеции аргини-на и/или созданию дефицита метаболитов этой аминокислоты, таких как NO и полиамины [14,16]. Однако противоопухолевое действие фер-мента может быть обусловлено также его анти-ангиогенной активностью.…”

Section: Introductionunclassified

“…A comparative analysis of anti-proliferative activity of original S. pyogenes M49-16 strain and its isogenic mutant with arginine deiminase gene deletion (M49-16delAD) was performed, using an endothelial EA.hy926 cell line. The bacterial supernatantes obtained by sonication of S. pyogenes M49- 16 and M49-16delAD were tested. The ability of S. pyogenes M49-16 and M49-16delAD supernatantes to hydrolyze arginine was assessed.…”

Section: A Role Of Arginine Deiminase From Streptococcus Pyogenes M49mentioning

confidence: 99%

A Role of Arginine Deiminase From Streptococcus Pyogenes M49-16 in Promoting Infection and Inhibition of Endothelial Cell Proliferation

Старикова¹,

Karaseva²,

Bürova³

et al. 2016

Med. immunol.

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“…[2,6,11,16,23,27]. ADI has also been known to inhibit the growth of melanoma and hepatocellular carcinoma cells in vitro as well as in vivo [19,20,24,26]. This anti-tumor activity of ADI has been attributed to the depletion of L-arginine, which is essential in these tumor cells [20,25].…”

mentioning

confidence: 99%

Growth Inhibition of Human Melanoma Cells by a Recombinant Arginine Deiminase Expressed in Escherichia coli

Kozai

Sasamori

Fujihara

et al. 2009

The Journal of Veterinary Medical Science

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ABSTRACT. We have cloned the arginine deiminase (ADI) gene from Mycoplasma hominis PG21 genomic DNA by polymerase chain reaction, and changed four TGA tryptophan codons (stop codon in E. coli) to TGG codons in the coding region by site-directed mutagenesis in order to express in E. coli. The recombinant ADI (rADI) was purified to apparent homogeneity by Ni-affinity chromatography after extraction from inclusion bodies followed by refolding. The rADI expressed in E. coli was estimated to be 50 kDa. Dimeric forms of rADI exerted enzymatic activity. We found that high concentration of potassium dihydrogenphosphate (PDP) and L-arginine addition in refolding reaction increases the enzyme activity. The specific activity of rADl was calculated as 0.618 U/mg. In addition, the enzyme activity of purified rADI remained for at least one month in 100 mM PDP solution (pH 6.5), but diminished within one week in 100 mM PDP solution (pH 7.4). Anti-tumor activity of the purified rADI was estimated to be 0.036 U/ml as 50% growth inhibitory activity against human melanoma cell line G-361. Arginine dehydrolysing mycoplasmas convert L-arginine into L-citrulline and ammonia by the arginine deiminase (ADI; EC 3.5.3.6) activity [1]. ADI gene of Mycoplasma hominis PG21 has been cloned in Escherichia coli by using plasmid pUC118 [7]. ADI has been shown to affect apoptosis and inhibit NO synthesis (i.e., anti-angiogenic effects), and exert effects against tumor necrosis factor- (TNF-) and neutralize endotoxin. [2,6,11,16,23,27]. ADI has also been known to inhibit the growth of melanoma and hepatocellular carcinoma cells in vitro as well as in vivo [19,20,24,26]. This anti-tumor activity of ADI has been attributed to the depletion of L-arginine, which is essential in these tumor cells [20,25]. Normal cells are not sensitive to external addition of ADI since they produce L-arginine by themselves. Expression of the ADI gene of M. homins PG21 in E. coli has been hampered since the ADI gene of M. hominis has four opal nonsense codons, which are known to encode tryptophan in mycoplasma cells. We have changed these opal codons to universal tryptophan codons and successfully expressed the recombinant ADI (rADI) gene of M. homins in E. coli, and demonstrated the enzymatic activity of purified rADI. MATERIALS AND METHODS Construction of ADI expression vector:Four stop codons TGA in the ADI gene cloned in pUC118 was changed into TGG by site-directed mutagenesis mediated by DpnImethod in order to express in E. coli [21]. Correct introductions of the mutation were confirmed by DNA sequencing. The mutated ADI gene, designated as SYN1903, was recloned into pET-47b (Novagen, Darmstadt, Germany) expression vector.Expression and purification of ADI: Recombinant pET47b plasmids encoding mycoplasmal ADI gene were transformed into competent E. coli BL21 (DE3) cells. The transformant was grown in 600 ml Luria broth (Sigma-Aldrich, St. Louis, MO, U.S.A.) at 30C, and isopropyl 1-thio--Dgalactoside was added at final concentration of 0.1 mM for induction of t...

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Arginine deiminase: a potential inhibitor of angiogenesis and tumour growth

Cited by 75 publications

References 33 publications

Arginine Deprivation as a Targeted Therapy for Cancer

Arginine Deprivation as a Targeted Therapy for Cancer

A Role of Arginine Deiminase From Streptococcus Pyogenes M49-16 in Promoting Infection and Inhibition of Endothelial Cell Proliferation

Growth Inhibition of Human Melanoma Cells by a Recombinant Arginine Deiminase Expressed in Escherichia coli

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