Recent developments in l-asparaginase discovery and its potential as anticancer agent

Shrivastava, Abhinav; Khan, Abdul Arif; Khurshid, Mohsin; Kalam, Mohd Abul; Jain, Shubha; Singhal, Pradeep K.

doi:10.1016/j.critrevonc.2015.01.002

Cited by 179 publications

(127 citation statements)

References 87 publications

Supporting

Mentioning

112

Contrasting

Unclassified

Order By: Relevance

“…51,52 Asparaginase, an enzyme, is an important chemotherapeutic agent for the management of acute leukemia and other blood-related cancers. 53 The mechanisms of asparaginase resistance include increased asparagine synthetase activity, genomic modulations and alterations, epigenetic changes, and so on. 54,55 Other miscellaneous drugs include hydroxyurea, procarbazine, and dacarbazine.…”

Section: Miscellaneous Agentsmentioning

confidence: 99%

Overcoming tumor cell chemoresistance using nanoparticles: lysosomes are beneficial for (stearoyl) gemcitabine-incorporated solid lipid nanoparticles

Chen¹,

Zheng²,

Shi³

et al. 2018

IJN

View full text Add to dashboard Cite

Despite recent advances in targeted therapies and immunotherapies, chemotherapy using cytotoxic agents remains an indispensable modality in cancer treatment. Recently, there has been a growing emphasis in using nanomedicine in cancer chemotherapy, and several nanomedicines have already been used clinically to treat cancers. There is evidence that formulating small molecular cancer chemotherapeutic agents into nanomedicines significantly modifies their pharmacokinetics and often improves their efficacy. Importantly, cancer cells often develop resistance to chemotherapy, and formulating anticancer drugs into nanomedicines also helps overcome chemoresistance. In this review, we briefly describe the different classes of cancer chemotherapeutic agents, their mechanisms of action and resistance, and evidence of overcoming the resistance using nanomedicines. We then emphasize on gemcitabine and our experience in discovering the unique (stearoyl) gemcitabine solid lipid nanoparticles that are effective against tumor cells resistant to gemcitabine and elucidate the underlying mechanisms. It seems that lysosomes, which are an obstacle in the delivery of many drugs, are actually beneficial for our (stearoyl) gemcitabine solid lipid nanoparticles to overcome tumor cell resistance to gemcitabine.

show abstract

Section: Miscellaneous Agentsmentioning

confidence: 99%

Overcoming tumor cell chemoresistance using nanoparticles: lysosomes are beneficial for (stearoyl) gemcitabine-incorporated solid lipid nanoparticles

Chen¹,

Zheng²,

Shi³

et al. 2018

IJN

View full text Add to dashboard Cite

show abstract

“…Due of its efficacy in selective killing of leukemic cells, it is also considered as a targeted therapy (Rizzari, 2013). But since the drug in present use bears many side effects (Barba, 2017;Shrivastava, 2016), researchers are in continuous search of new sources for this enzyme. The non-immunological side effects of this enzyme can be mitigated by the discovery of new sources for L-Asparaginase enzyme and its characterization (Ali, 2016).…”

Section: Introductionmentioning

confidence: 99%

Isolation Screening and Identification of Bacterial Endophytes from Medicinal Plants as a potential source of L-Asparaginase Enzyme

Abhini¹,

K²

2018

JCHPS

View full text Add to dashboard Cite

L-Asparaginase is an enzyme (EC3.5.1.1) used as chemotherapeutic agent for the treatment of Acute Lymphoblastic Leukemia (ALL). The commercial L-Asparaginase now available is of bacterial origin and since it shows many side effects, search for alternative sources of this enzyme is highly necessary, owing to its high therapeutic significance. In the present study an attempt has been made to isolate bacterial endophytes, with L-Asparaginase potentiality, from medicinal plants. From 16 different medicinal plants 127 bacterial endophytes have been isolated, among which 51 endophytes were capable of producing L-Asparaginase enzyme. Two isolates that showed excellent enzyme activity as 1.436 U/ml and 1.827 U/ml were identified, based on biochemical tests and 16s rRNA gene sequencing, as Acinetobacter baumannii and Bacillus subtilis which were isolated from the medicinal plants, Annona muricata and Averrhoa carambola respectively. The phylogenetic tree for the two isolates were constructed based on the 16s rRNA blast results and the 16s rRNA gene sequences were deposited in gene bank and accession numbers were received.

show abstract

“…L-asparaginase isolated from E. coli and Erwinia carotovora is used for the clinical treatment of ALL but it suffers from a number of side-effects such as resistance, premature inactivation, allergic reaction, shorter drug duration and easy clearance from body 8,9 . Therefore, alternative sources such as plant enzyme are being searched for the isolation of L-asparaginase 10,2 . As compared to bacterial L-asparaginase plant enzyme has been not explored widely.…”

Section: Introductionmentioning

confidence: 99%

“…Acute Lymphoblastic Leukemia is a type of cancer in children arising due to expansion of lymphoid blasts and monoclonal proliferation in blood and bone marrow 1,2 . L-asparaginase synthetase is the only known enzyme for the synthesis of asparagine in cells.…”

Section: Introductionmentioning

confidence: 99%

Comparative Characterization of L-Asparaginase Extracted From Plant and Microbial Sources

Kaur¹,

Kumar²,

Kumar³

2017

Int. J. Res. Ayurveda Pharm.

View full text Add to dashboard Cite

L-asparaginase has been used for the treatment of different leukemia such as Acute Lymphoblastic Leukemia. Unlike normal cells leukemic cells cannot synthesize asparagine on their own. Therefore, when L-asparaginase is injected into blood it breaks down asparagine to aspartic acid and ammonia and hence tumor cells die due to asparagine starvation. It is produced by both microbes as well as plants. Therefore, in the present study we compared the L-asparaginase extracted from plants as well as microbes. Among the plants S. nigrum showed the highest activity (52 IU/ml) whereas among microbes B. subtilis (MTCC-121) had the highest activity (43.11 IU/ml). Both the enzymes were kinetically characterized and it was found that plant enzyme was stable over pH and temperature variations. The effect of metal ions was same on both the enzymes whereas chelators enhanced the plant enzyme whereas had no effect on microbial enzyme. Plant enzyme showed the highest activity and was more stable to the environmental variations as compared to microbial enzyme.

show abstract

Recent developments in l-asparaginase discovery and its potential as anticancer agent

Cited by 179 publications

References 87 publications

Overcoming tumor cell chemoresistance using nanoparticles: lysosomes are beneficial for (stearoyl) gemcitabine-incorporated solid lipid nanoparticles

Overcoming tumor cell chemoresistance using nanoparticles: lysosomes are beneficial for (stearoyl) gemcitabine-incorporated solid lipid nanoparticles

Isolation Screening and Identification of Bacterial Endophytes from Medicinal Plants as a potential source of L-Asparaginase Enzyme

Comparative Characterization of L-Asparaginase Extracted From Plant and Microbial Sources

Contact Info

Product

Resources

About