Antitumor activity of L-asparaginase from Erwinia Carotovora from against different leukemic and solid tumours cell lines

OIu, Abakumova; Ov, Podobed; Pa, Karalkin; Li, Kondakova; Nn, Sokolov

doi:10.18097/pbmc20135905498

Cited by 15 publications

(5 citation statements)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…So rASPG is highly specific for the substrate L-asparagine. Abakumova et al (2013) provided convincing evidence that L-asparaginase induced apoptosis as its principal process of causing death of leukemic and solid tumor cells (Abakumova et al, 2013). In our study, four tumor cell lines with increasing amounts of rASPG resulted in a significant increase in the number of dead cells (Table 6).…”

Section: Concentration Of Dmso (%)supporting

confidence: 66%

Optimization, purification and characterization of recombinant L-asparaginase II in Escherichia coli

Nguyen¹,

Nguyen²,

Nguyen³

et al. 2016

Afr. J. Biotechnol.

View full text Add to dashboard Cite

We studied optimal L-asparaginase sequence from GenBank accession number X12746 encoding for Lasparaginase from Erwinia chrysanthemi NCPPB1125. The expression level of recombinant Lasparaginase was determined as 78% of the total proteins. The purified L-asparaginase had a molecular mass of 37 kDa with specific activity of 312.8 U/mg. Kinetic parameters, K m , V max , K cat and K cat /K m of purified enzyme were found to be 0.5 mM, 500 U/mg, 14.9  10 3 s-1 , and 29.9  10 3 mM-1 s-1 , respectively. Temperature and pH optimum were observed at 45ºC and pH 7.5, respectively. The enzyme exhibited about 20 and 60% retention of activity following 100 min incubation at 55 or 40°C, respectively. The activity of enzyme was inhibited by EDTA, Hg 2+ , Cu 2+ , Ni 2+ , and enhanced by Mg 2+. Detergents (Tween 20, Tween 80, Triton X-100, and Triton X-114) decreased enzyme activity. DTT and DMSO at appropriate concentrations enhanced enzyme activity. In vitro anti-cancer activity was performed using different tumor cell lines. Concentration of recombinant L-asparaginase at 50 µg/ml inhibited 45.32, 48.22, 53.68, 51.22% with HL-60, P388, P3X63Ag8, SP2/0-Ag14 cell lines. Recombinant L-asparaginase was expressed successfully in Escherichia coli with high expression level, had a high specific activity and antiproliferative effect on several tumor cell lines.

show abstract

Section: Concentration Of Dmso (%)supporting

confidence: 66%

Optimization, purification and characterization of recombinant L-asparaginase II in Escherichia coli

Nguyen¹,

Nguyen²,

Nguyen³

et al. 2016

Afr. J. Biotechnol.

View full text Add to dashboard Cite

show abstract

“…Autophagy, the stress activated catabolism of macromolecules and even complete organelles in order to preserve and recycle energy and nutrients is a potent rescue mechanism for cells to overcome periods of limited availability of resources [57]. ASNase is known to induce cytoprotective autophagy in ovarian cancer, chronic myeloid leukemia (CML), and ALL [57] and also ADI therapy FLT3 tyrosine kinase inhibitor [75] Notch inhibition [76] Glucose metabolism [77,78] Modulators of the integrated stress response [64] mTORC1 [55,65] Metformin [66] Asparagine Doxorubicin [79] BH3 mimetics [80] KRAS pathway inhibition [56] Chloroquine [57] Targeting Gln metabolism [60] GCN2 inhibition [81] GLS inhibition [60,62] ZBTB1 [72] Wnt/STOP signaling [73] Metformin [67] Arginine Cytarabine [26] Histone-deacetylase inhibitor (SAHA) [82] Chloroquine [58] Targeting Gln metabolism [61,63] Methionine Fluorouracil [83] Doxorubicin [84] Vincristine [84] BCNU [33] Temozolomide [33] Cisplatin [85] TRAIL-R2 agonist [86] Leucine Epidermal growth factor receptor (EGFR) inhibitors [87] Tamoxifen [88] Cysteine BSO [40] Curcumin [40] Trends in Endocrinology & Metabolism…”

Section: Trends In Endocrinology and Metabolismmentioning

confidence: 99%

Amino Acid Depletion Therapies: Starving Cancer Cells to Death

Butler

Meer

Leeuwen

2021

Trends in Endocrinology & Metabolism

156

124

View full text Add to dashboard Cite

Targeting tumor cell metabolism is an attractive form of therapy, as it may enhance treatment response in therapy resistant cancers as well as mitigate treatment-related toxicities by reducing the need for genotoxic agents. To meet their increased demand for biomass accumulation and energy production and to maintain redox homeostasis, tumor cells undergo profound changes in their metabolism. In addition to the diversion of glucose metabolism, this is achieved by upregulation of amino acid metabolism. Interfering with amino acid availability can be selectively lethal to tumor cells and has proven to be a cancer specific Achilles' heel. Here we review the biology behind such cancer specific amino acid dependencies and discuss how these vulnerabilities can be exploited to improve cancer therapies.

show abstract

“…L-asparaginase also synergizes with other drugs to give enhanced anti-cancer effect. Doxorubicin together with L-asparaginase significantly increased the number of cell death in breast cancer in vitro [ 78 ]. L-asparaginase in combination with temozolomide suppressed subcutaneous glioma growth in mice [ 79 ].…”

Section: Asparagine Starvation As An Anti-cancer Strategymentioning

confidence: 99%

Drug-induced amino acid deprivation as strategy for cancer therapy

2017

View full text Add to dashboard Cite

Cancer is caused by uncontrollable growth of neoplastic cells, leading to invasion of adjacent and distant tissues resulting in death. Cancer cells have specific nutrient(s) auxotrophy and have a much higher nutrient demand compared to normal tissues. Therefore, different metabolic inhibitors or nutrient-depleting enzymes have been tested for their anti-cancer activities. We review recent available laboratory and clinical data on using various specific amino acid metabolic pathways inhibitors in treating cancers. Our focus is on glutamine, asparagine, and arginine starvation. These three amino acids are chosen due to their better scientific evidence compared to other related approaches in cancer treatment. Amino acid-specific depleting enzymes have been adopted in different standard chemotherapy protocols. Glutamine starvation by glutaminase inhibitior, transporter inhibitor, or glutamine depletion has shown to have significant anti-cancer effect in pre-clinical studies. Currently, glutaminase inhibitor is under clinical trial for testing anti-cancer efficacy. Clinical data suggests that asparagine depletion is effective in treating hematologic malignancies even as a single agent. On the other hand, arginine depletion has lower toxicity profile and can effectively reduce the level of pro-cancer biochemicals in patients as shown by ours and others’ data. This supports the clinical use of arginine depletion as anti-cancer therapy but its exact efficacy in various cancers requires further investigation. However, clinical application of these enzymes is usually hindered by common problems including allergy to these foreign proteins, off-target cytotoxicity, short half-life and rapidly emerging chemoresistance. There have been efforts to overcome these problems by modifying the drugs in different ways to circumvent these hindrance such as (1) isolate human native enzymes to reduce allergy, (2) isolate enzyme isoforms with higher specificities and efficiencies, (3) pegylate the enzymes to reduce allergy and prolong the half-lives, and (4) design drug combinations protocols to enhance the efficacy of chemotherapy by drug synergy and minimizing resistance. These improvements can potentially lead to the development of more effective anti-cancer treatment with less adverse effects and higher therapeutic efficacy.

show abstract

Antitumor activity of L-asparaginase from Erwinia Carotovora from against different leukemic and solid tumours cell lines

Cited by 15 publications

References 12 publications

Optimization, purification and characterization of recombinant L-asparaginase II in Escherichia coli

Optimization, purification and characterization of recombinant L-asparaginase II in Escherichia coli

Amino Acid Depletion Therapies: Starving Cancer Cells to Death

Drug-induced amino acid deprivation as strategy for cancer therapy

Contact Info

Product

Resources

About