scholarly journals Therapeutic L-Asparaginase Activity of Bacteria Isolated from Marine Sediments

2016 ◽  
Vol 8 (04) ◽  
Author(s):  
J. K. Arjun ◽  
B. Aneesh ◽  
T. Kavitha ◽  
K. Krishnan
Keyword(s):  
Marine Bacteria ◽  
Therapeutic Potential ◽  
Lymphoblastic Leukemia ◽  
Extracellular Enzyme ◽  
Hl60 Cell ◽  
Bacillus Sp ◽  
Diverse Range ◽  
Term Administration ◽  
Asparaginase Activity ◽  
Hl60 Cell Line

L-Asparaginase, a therapeutic enzyme used in lymphoblastic leukemia and lymphosarcoma chemotherapy which is derived mostly from the bacterial sources Escherichia coli and Erwinia sp. The long term administration of the drug leads to the development of resistant tumours and anaphylactic shock in certain individuals. Hence serologically different L-Asparaginase from novel microbial sources with enhanced therapeutic potential and immunological characteristics is an essential requirement. The marine bacteria having diverse range of potential enzymes might be a source for L-Asparaginase with novel properties, which are still unexplored. In this study, we have screened marine bacteria isolated from the coastal regions of Kerala which showed both intra and extra cellular L-Asparaginase activity. Bacillus sp. (Accession no KF142395) was found to have the highest extracellular enzyme activity (2.31 IU/ml) while Shewanella sp. (Accession no KF142390) showed maximum intracellular Asparaginase activity (2.16 IU/ml).The crude extracellular enzyme preparation from Bacillus sp. had cytotoxic effect on HL60 cell line with an IC50 value of 12.5µg/ml.

scholarly journals Crizotinib acts as ABL1 inhibitor combining ATP-binding with allosteric inhibition and is active against native BCR-ABL1 and its resistance and compound mutants BCR-ABL1T315I and BCR-ABL1T315I-E255K

2021 ◽  
Author(s):  
Afsar Ali Mian ◽  
Isabella Haberbosch ◽  
Hazem Khamaisie ◽  
Abed Agbarya ◽  
Larissa Pietsch ◽  
...  
Keyword(s):  
Binding Site ◽  
Kinase Inhibitors ◽  
Therapeutic Potential ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Binding Pocket ◽  
Atp Binding ◽  
Atp Binding Site ◽  
Lung Cancer Patients

AbstractResistance remains the major clinical challenge for the therapy of Philadelphia chromosome–positive (Ph+) leukemia. With the exception of ponatinib, all approved tyrosine kinase inhibitors (TKIs) are unable to inhibit the common “gatekeeper” mutation T315I. Here we investigated the therapeutic potential of crizotinib, a TKI approved for targeting ALK and ROS1 in non-small cell lung cancer patients, which inhibited also the ABL1 kinase in cell-free systems, for the treatment of advanced and therapy-resistant Ph+ leukemia. By inhibiting the BCR-ABL1 kinase, crizotinib efficiently suppressed growth of Ph+ cells without affecting growth of Ph− cells. It was also active in Ph+ patient-derived long-term cultures (PD-LTCs) independently of the responsiveness/resistance to other TKIs. The efficacy of crizotinib was confirmed in vivo in syngeneic mouse models of BCR-ABL1- or BCR-ABL1T315I-driven chronic myeloid leukemia–like disease and in BCR-ABL1-driven acute lymphoblastic leukemia (ALL). Although crizotinib binds to the ATP-binding site, it also allosterically affected the myristol binding pocket, the binding site of GNF2 and asciminib (former ABL001). Therefore, crizotinib has a seemingly unique double mechanism of action, on the ATP-binding site and on the myristoylation binding pocket. These findings strongly suggest the clinical evaluation of crizotinib for the treatment of advanced and therapy-resistant Ph+ leukemia.

scholarly journals Bis[Pyrrolyl Ru(II)] Triads: a New Class of Photosensitizers for Metal-Organic Photodynamic Therapy

2020 ◽  
Author(s):  
Deborah A. Smithen ◽  
Susan Monro ◽  
Mitch Pinto ◽  
John A. Roque III ◽  
Roberto M. Diaz-Rodriguez ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Visible Light ◽  
Red Light ◽  
Visible Region ◽  
Hl60 Cell ◽  
Quantum Yields ◽  
Human Leukemia ◽  
New Family ◽  
Hl60 Cell Line

A new family of ten dinuclear Ru(II) complexes based on the bis[pyrrolyl Ru(II)] triad scaffold, where two Ru(bpy)<sub>2</sub> centers are separated by a variety of organic linkers, was prepared to evaluate the influence of the organic chromophore on the spectroscopic and in vitro photodynamic therapy (PDT) properties of the compounds. The bis[pyrrolyl Ru(II)] triads absorbed strongly throughout the visible region, with several members having molar extinction coefficients (e) ≥10<sup>4</sup> at 600–620 nm and longer. Phosphorescence quantum yields were generally less than 0.1% and in some cases undetectable. The singlet oxygen quantum yields ranged from 5% to 77% and generally correlated with their photocytotoxicities toward human leukemia (HL-60) cells regardless of the wavelength of light used. Dark cytotoxicities varied ten-fold, with EC<sub>50</sub> values in the range of 10–100 µM and phototherapeutic indices (PIs) as large as 5,400 and 260 with broadband visible (28 J cm<sup>-2</sup>, 7.8 mW cm<sup>-2</sup>) and 625-nm red (100 J cm<sup>-2</sup>, 42 mW cm<sup>-2</sup>) light, respectively. The bis[pyrrolyl Ru(II)] triad with a pyrenyl linker (5h) was especially potent, with an EC50 value of 1 nM and PI >27,000 with visible light and subnanomolar activity with 625-nm light (100 J cm<sup>-2</sup>, 28 mW cm<sup>-2</sup>). The lead compound 5h was also tested in a tumor spheroid assay using the HL60 cell line and exhibited greater photocytotoxcicity in this more resistant model (EC<sub>50</sub>=60 nM and PI>1,200 with 625-nm light) despite a lower dark cytotoxicity. The in vitro PDT effects of 5h extended to bacteria, where submicromolar EC<sub>50</sub> values and PIs >300 against <i>S. mutans</i> and <i>S. aureus </i>were obtained with visible light. This activity was attenuated with 625-nm red light, but PIs were still near 50. The ligand-localized <sup>3</sup>ππ* state contributed by the pyrenyl linker of 5h likely plays a key role in its phototoxic effects toward cancer cells and bacteria.<br><br>

scholarly journals PRODUCTION AND CHARACTERIZATION OF CHITINASE ENZYMES FROM SULILI HOT SPRING IN SOUTH SULAWESI, Bacillus sp. HSA,3-1a

2010 ◽  
Vol 10 (2) ◽  
pp. 256-260 ◽  
Author(s):  
Hasnah Natsir ◽  
Abd. Rauf Patong ◽  
Maggy Thenawidjaja Suhartono ◽  
Ahyar Ahmad
Keyword(s):  
Hot Spring ◽  
Thermophilic Bacteria ◽  
Extracellular Enzyme ◽  
Colloidal Chitin ◽  
Bacillus Sp ◽  
Optimum Temperature ◽  
South Sulawesi ◽  
Sds Page ◽  
Physiological Analysis

Chitinase is an extracellular enzyme which is capable in hydrolyzing insoluble chitin to its oligomeric and monomeric components. The enzyme produced by thermophilic bacteria was screened and isolated from Sulili hot spring in Pinrang, South Sulawesi, Indonesia. The gram positive spore forming rod shape bacteria was identified as Bacillus sp. HSA,3-1a through morphological and physiological analysis. The production of chitinase enzyme was conducted at various concentration of colloidal chitin at a pH of 7.0 and a temperature of 55 °C. The bacteria optimally was produced the enzyme at a colloidal chitin concentration of 0.5% after 72 h of incubation. The optimum temperature, pH and substrate concentration of chitinase were 60 °C, 7.0 and 0.3%, respectively. The enzyme was stable at a pH of 7.0 and a temperature of 60 °C after 2 h of incubation. The chitinase activities was increased by addition of 1 mM Mg2+, Ca2+ and Mn2+ ions, whereas the activities were  decreased by 1 mM Co2+, Fe2+ and Zn2 ions. The molecular weight of the crude enzyme was determined using SDS-PAGE analysis. Five protein fractions were obtained from SDS-PAGE, with MWs of 79, 71, 48, 43 and 22 kDa.   Keywords: colloidal chitin, thermophilic bacteria, chitinase

scholarly journals Down-Regulation of Interleukin-8 Gene Expression in HL60 Cell Line by Human Kunitz-Type Trypsin Inhibitor

1995 ◽  
Vol 206 (3) ◽  
pp. 927-934 ◽  
Author(s):  
K. Maehara ◽  
N. Kanayama ◽  
A. Halim ◽  
E. Elmaradny ◽  
T. Oda ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Line ◽  
Trypsin Inhibitor ◽  
Interleukin 8 ◽  
Hl60 Cell ◽  
Down Regulation ◽  
Kunitz Type ◽  
Hl60 Cell Line

Isolation, Characterization and Application of Protease Enzyme from Marine Bacteria

2021 ◽  
pp. 4236-4240
Author(s):  
Sneha S ◽  
Mrunal Palsokar ◽  
Vemula Sai Jahnavi ◽  
Anwesha Sarkar ◽  
K. V. Bhaskara Rao
Keyword(s):  
Marine Bacteria ◽  
Peptide Bond ◽  
Mangrove Sediment ◽  
Bacillus Sp ◽  
Bacterial Isolates ◽  
Sediment Samples ◽  
Protease Enzyme ◽  
Stain Removal ◽  
Marine Sediment Sample ◽  
Protease Assay

Protease constitutes the major group of catalytic enzymes which is involved in hydrolyzing peptide bond of proteins. Marine sediment sample were collected and protease producing bacterial isolates were identified by using casein as a substrate. The organisms were characterized by biochemical test and identified as Bacillus sp. In order to check for the production of protease enzyme, quantitative protease assay and Lowry’s method of protein estimation was carried out. The crude extract of protease was subjected for blood stain removal activity and the enzyme proved to be efficient which removed the stain in 15 min. The purpose of the current study is to isolate, identify, characterize and to carry out applications of protease enzyme from marine bacteria isolated from mangrove sediment samples.

scholarly journals Trastuzumab-Targeted Biodegradable Nanoparticles for Enhanced Delivery of Dasatinib in HER2+ Metastasic Breast Cancer

Nanomaterials ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 1793 ◽  
Author(s):  
Enrique Niza ◽  
María del Mar Noblejas-López ◽  
Iván Bravo ◽  
Cristina Nieto-Jiménez ◽  
José Antonio Castro-Osma ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Therapy ◽  
Therapeutic Potential ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Breast Cancer Cell Lines ◽  
Her2 Positive ◽  
Multikinase Inhibitor ◽  
Biodegradable Nanoparticles

Dasatinib (DAS) is a multikinase inhibitor that acts on several signaling kinases. DAS is used as a second-line treatment for chronic accelerated myeloid and Philadelphia chromosome-positive acute lymphoblastic leukemia. The therapeutic potential of DAS in other solid tumours is under evaluation. As for many other compounds, an improvement in their pharmacokinetic and delivery properties would potential augment the efficacy. Antibody-targeted biodegradable nanoparticles can be useful in targeted cancer therapy. DAS has shown activity in human epidermal growth factor receptor 2 (HER2) positive tumors, so conjugation of this compound with the anti-HER2 antibody trastuzumab (TAB) with the use of nanocarriers could improve its efficacy. TAB-targeted DAS-loaded nanoparticles were generated by nanotechnology. The guided nanocarriers enhanced in vitro cytotoxicity of DAS against HER2 human breast cancer cell lines. Cellular mechanistic, release studies and nanoparticles stability were undertaken to provide evidences for positioning DAS-loaded TAB-targeted nanoparticles as a potential strategy for further development in HER2-overexpressing breast cancer therapy.

Effect of bixin on DNA damage and cell death induced by doxorubicin in HL60 cell line

2016 ◽  
Vol 35 (12) ◽  
pp. 1319-1327 ◽  
Author(s):  
GC Santos ◽  
MR Almeida ◽  
LMG Antunes ◽  
MLP Bianchi
Keyword(s):  
Dna Damage ◽  
Hl60 Cell ◽  
Red Pigment ◽  
Combined Treatments ◽  
Therapeutic Approaches ◽  
Cytotoxic Effects ◽  
Hl60 Cells ◽  
Apoptotic Effect ◽  
Induction Of Apoptosis ◽  
Hl60 Cell Line

Bixin is a natural red pigment extracted from annatto. Although it is widely used as a coloring agent in food, there are few studies about the effect of this carotenoid on DNA. This study aimed to investigate the effects of bixin on cytotoxicity and genotoxicity induced by doxorubicin in HL60 cells. At concentrations above 0.3 μg/mL, bixin demonstrated cytotoxic effects in HL60 cells. Furthermore, this carotenoid was neither mutagenic nor genotoxic to HL60 cells and reduced the DNA damage induced by doxorubicin. Bixin and doxorubicin showed no apoptotic effect in HL60 cells, but the simultaneous combined treatments showed an increase in the percentage of apoptotic cells. In conclusion, our results showed that bixin modulates the cytotoxicity of doxorubicin via induction of apoptosis. The results of this study provide more knowledge about the toxic effects of anticancer treatments and how the natural compounds can be useful on these therapeutic approaches.

scholarly journals Highly efficient novel recombinant L-asparaginase with no glutaminase activity from a new halo-thermotolerant Bacillus strain

Bioimpacts ◽  
2018 ◽  
Vol 9 (1) ◽  
pp. 15-23 ◽  
Author(s):  
Azam Safary ◽  
Rezvan Moniri ◽  
Maryam Hamzeh-Mivehroud ◽  
Siavoush Dastmalchi
Keyword(s):  
Lymphoblastic Leukemia ◽  
Industrial Applications ◽  
Biochemical Properties ◽  
Substrate Affinity ◽  
Bacillus Sp ◽  
Recombinant Enzymes ◽  
E Coli ◽  
Bacillus Strain ◽  
Antineoplastic Effect ◽  
Wide Range

Introduction: The bacterial enzyme has gained more attention in therapeutic application because of the higher substrate specificity and longer half-life. L-asparaginase is an important enzyme with known antineoplastic effect against acute lymphoblastic leukemia (ALL). Methods: Novel L-asparaginase genes were identified from a locally isolated halo-thermotolerant Bacillus strain and the recombinant enzymes were overexpressed in modified E. coli strains, OrigamiTM B and BL21. In addition, the biochemical properties of the purified enzymes were characterized, and the enzyme activity was evaluated at different temperatures, pH, and substrate concentrations. Results: The concentration of pure soluble enzyme obtained from Origami strain was ~30 mg/L of bacterial culture, which indicates the significant improvement compared to L-asparaginase produced by E. coli BL21 strain. The catalytic activity assay on the identified L-asparaginases (ansA1 and ansA3 genes) from Bacillus sp. SL-1 demonstrated that only ansA1 gene codes an active and stable homologue (ASPase A1) with high substrate affinity toward L-asparagine. The Kcat and Km values for the purified ASPase A1 enzyme were 23.96s-1 and 10.66 µM, respectively. In addition, the recombinant ASPase A1 enzyme from Bacillus sp. SL-1 possessed higher specificity to L-asparagine than L-glutamine. The ASPase A1 enzyme was highly thermostable and resistant to the wide range of pH 4.5–10. Conclusion: The biochemical properties of the novel ASPase A1 derived from Bacillus sp. SL-l indicated a great potential for the identified enzyme in pharmaceutical and industrial applications.

scholarly journals Resveratrol Protects Against Methotrexate-Induced Hepatic Injury in Rats

2010 ◽  
Vol 13 (2) ◽  
pp. 303 ◽  
Author(s):  
Tugba Tunalı-Akbay ◽  
Ozer Sehirli ◽  
Feriha Ercan ◽  
Goksel Sener
Keyword(s):  
Aspartate Aminotransferase ◽  
Alanine Aminotransferase ◽  
Hepatic Injury ◽  
Therapeutic Potential ◽  
Lymphoblastic Leukemia ◽  
Treated Group ◽  
Serum Samples ◽  
Plasma Parameters ◽  
Lactate Dehydrogenase Activity ◽  
Tnf Α

Purpose. The aim of this study to investigate the possible protective effect of resveratrol on some liver and serum/plasma parameters in methotrexate induced toxicity in rats. Methotrexate is used widely to treat various neoplastic diseases such as acute lymphoblastic leukemia, lymphoma, solid cancers, and autoimmune diseases. We hypothesized that resveratrol has a potential to decrease the oxidant damage in MTX-induced hepatic injury. Methods. Following a single dose of methotrexate (20 mg/kg, i.p.), either saline or resveratrol (10 mg/kg, orally) was administered for 5 days. After decapitation of the rats, trunk blood was obtained and the liver was removed to measure malondialdehyde and glutathione levels, myeloperoxidase and thromboplastic activities and collagen content. Aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase activity were measured in the serum samples, while TNF-α and total antioxidant capacity were assayed in plasma samples. Results. Our results showed that MTX administration increased the hepatic malondialdehyde levels, myeloperoxidase and thromboplastic activities and collagen contents and decreased glutathione, while these alterations were reversed in resveratrol-treated group. Elevated aspartate aminotransferase and alanine aminotransferase activities and TNF-α level observed following MTX treatment was depressed with resveratrol. Conclusions. The present study showed that resveratrol protects against methotrexate-induced hepatic injury and may be of therapeutic potential in alleviating the systemic side effects of chemotherapeutics.

Sign in / Sign up

Export Citation Format

Share Document