Effect of Chicken Bone Extracts on Metabolic and Mitochondrial Functions of K562 Cell Line

Background: Tetracyclines’ use in intensive animal farming has raised some concerns regarding the biosafety for humans. Increasing evidences have revealed the presence of these drugs in processed animal by-products, such as bone, throughout the food chain. A potential off-target of tetracyclines is the bacterial-like mitochondrial translational machinery, thereby causing proteostatic alterations in mitochondrial DNA-encoded components of the oxidative phosphorylation system. Methods: The Seahorse methodology, confocal microscopy imaging of mitochondrial potential and reactive oxygen species, and q-RT-PCR analysis of the expression of genes involved in mitochondrial biogenesis and mitophagy were carried out on human lymphoblast derived K562 cell line challenged with bone powder derived from chicken treated with or without oxytetracycline and pure oxytetracycline. Results: A complex dose-dependent profile was attained with a low dosage of bone powder extracts causing a metabolic adaptation hallmarked by stimulation of the mitochondrial respiration and enhanced expression of mitochondriogenic factors in particular in cells challenged with oxytetracycline-free bone extract. Conversely, a higher dosage of bone powder extracts, regardless of their source, caused a progressive inhibition of mitochondrial respiration and glycolysis, ultimately leading to cell death. No significant effects of the pure oxytetracycline were observed. Conclusion: Bone powder, regardless of chicken treatment, contains and releases factors/chemicals responsible for the observed effects on energy metabolism. Quantitative differential effects appear to depend on biochemical alterations in the bone matrix caused by antibiotics rather than antibiotics themselves.

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A New Series of Antileukemic Agents: Design, Synthesis, In Vitro and In Silico Evaluation of Thiazole-Based ABL1 Kinase Inhibitors

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520620666200824100408 ◽

2020 ◽

Vol 20 ◽

Author(s):

Ebru Zeytün ◽

Mehlika D. Altıntop ◽

Belgin Sever ◽

Ahmet Özdemir ◽

Doha E. Ellakwa ◽

...

Keyword(s):

Molecular Docking ◽

Anticancer Activity ◽

Cell Line ◽

Antiproliferative Activity ◽

In Silico ◽

K562 Cell ◽

Kinase Inhibitors ◽

K562 Cell Line ◽

Cytotoxic Effects ◽

Atp Binding Site

Background: After the milestone approval of imatinib, more than 25 antitumor agents targeting kinases have been approved, and several promising candidates are in various stages of clinical evaluation. Objectives : Due to the importance of thiazole scaffold in targeted anticancer drug discovery, the goal of this work is the design of new thiazolyl hydrazones as potent ABL1 kinase inhibitors for the management of chronic myeloid leukemia (CML). Methods: New thiazolyl hydrazones (2a-p) were synthesized and investigated for their cytotoxic effects on K562 CML cell line. Compounds 2h, 2j and 2l showed potent anticancer activity against K562 cell line. The cytotoxic effects of these compounds on other leukemia (HL-60, MT-2 and Jurkat) and HeLa human cervical carcinoma cell lines were also investigated. Furthermore, their cytotoxic effects on mitogen-activated peripheral blood mononuclear cells (MA-PBMCs) were evaluated to determine their selectivity. Due to its selective and potent anticancer activity, compound 2j was benchmarked for its apoptosis-inducing potential on K562 cell line and inhibitory effects on eight different tyrosine kinases (TKs) including ABL1 kinase. In order to investigate the binding mode of compound 2j into the ATP binding site of ABL1 kinase (PDB: 1IEP), molecular docking study was conducted using MOE 2018.01 program. The QikProp module of Schrödinger’s Molecular modelling package was used to predict the pharmacokinetic properties of compounds 2a-p. Results: 4-(4-(Methylsulfonyl)phenyl)-2-[2-((1,3-benzodioxol-4-yl)methylene)hydrazinyl]thiazole (2j) showed antiproliferative activity against K562 cell line with an IC50 value of 8.87±1.93 µM similar to imatinib (IC50= 6.84±1.11 µM). Compound 2j was found to be more effective than imatinib on HL-60, Jurkat and MT-2 cells. Compound 2j also showed cytotoxic activity against HeLa cell line similar to imatinib. The higher selectivity index value of compound 2j than imatinib indicated that its antiproliferative activity was selective. Compound 2j also induced apoptosis in K562 cell line more than imatinib. Among eight TKs, compound 2j showed the strongest inhibitory activity against ABL1 kinase enzyme (IC50= 5.37±1.17 µM). According to molecular docking studies, compound 2j exhibited high affinity to the ATP binding site of ABL1 kinase forming significant intermolecular interactions. On the basis of in silico studies, this compound did not violate Lipinski's rule of five and Jorgensen's rule of three. Conclusion: Compound 2j stands out as a potential orally bioavailable ABL1 kinase inhibitor for the treatment of CML.

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Optimization of differentiation condition for K562 cell line and rat erythroleukemia cell line

Toxicology Letters ◽

10.1016/j.toxlet.2018.06.1030 ◽

2018 ◽

Vol 295 ◽

pp. S251

Author(s):

M. Otani ◽

K. Iwashita ◽

T. Utsumi ◽

S. Kawamura

Keyword(s):

Cell Line ◽

K562 Cell ◽

K562 Cell Line ◽

Erythroleukemia Cell

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Overexpression of transglutaminase 2 accelerates the erythroid differentiation of human chronic myelogenous leukemia K562 cell line through PI3K/Akt signaling pathway

FEBS Letters ◽

10.1016/j.febslet.2004.10.031 ◽

2004 ◽

Vol 577 (3) ◽

pp. 361-366 ◽

Cited By ~ 16

Author(s):

Sung-Koo Kang ◽

Ji-Young Lee ◽

Tae-Wook Chung ◽

Cheorl-Ho Kim

Keyword(s):

Cell Line ◽

K562 Cell ◽

Transglutaminase 2 ◽

Erythroid Differentiation ◽

Akt Signaling ◽

Myelogenous Leukemia ◽

Akt Signaling Pathway ◽

K562 Cell Line ◽

Human Chronic Myelogenous Leukemia ◽

Leukemia K562 Cell

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Tyrosine Kinase Inhibitor STI571 (Imatinib) Cooperates with Wild-Type p53 on K562 Cell Line to Enhance Its Proapoptotic Effects

Acta Haematologica ◽

10.1159/000087889 ◽

2005 ◽

Vol 114 (3) ◽

pp. 150-154 ◽

Cited By ~ 2

Author(s):

Gianluca Brusa ◽

Manuela Mancini ◽

Fabio Campanini ◽

Alberto Calabrò ◽

Elisa Zuffa ◽

...

Keyword(s):

Tyrosine Kinase ◽

Tyrosine Kinase Inhibitor ◽

Cell Line ◽

K562 Cell ◽

Kinase Inhibitor ◽

Wild Type ◽

K562 Cell Line ◽

Wild Type P53

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Modification by Heme Oxygenase Inhibitor, Tin Protoporphyrin, of Cellular Differentiation of Human Myeloid Leukemia K562 Cell Line.

Biological and Pharmaceutical Bulletin ◽

10.1248/bpb.22.439 ◽

1999 ◽

Vol 22 (4) ◽

pp. 439-440 ◽

Cited By ~ 1

Author(s):

Yukiko KOISO ◽

Yasuyuki FUJIMOTO ◽

Daisuke MATSUMURA ◽

Osamu NAKAJIMA ◽

Yuichi HASHIMOTO

Keyword(s):

Cell Line ◽

Heme Oxygenase ◽

K562 Cell ◽

Myeloid Leukemia ◽

Cellular Differentiation ◽

K562 Cell Line ◽

Tin Protoporphyrin ◽

Leukemia K562 Cell

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Molecular and cytological investigations of phosphoglucomutase (PGM1) in the K562 cell line

Annals of Human Genetics ◽

10.1046/j.1469-1809.1997.6120099.x ◽

1997 ◽

Vol 61 (2) ◽

pp. 99-108 ◽

Cited By ~ 1

Author(s):

J. TOMKINS ◽

M. FOX ◽

J. U. LOVEGROVE ◽

J. PARRINGTON ◽

D. A. HOPKINSON ◽

...

Keyword(s):

Cell Line ◽

K562 Cell ◽

K562 Cell Line

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Absorption Characteristics of Combination Medication of Realgar and Indigo Naturalis: In Vitro Transport across MDCK-MDR1 Cells and In Vivo Pharmacokinetics in Mice after Oral Administration

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2018/6493630 ◽

2018 ◽

Vol 2018 ◽

pp. 1-10 ◽

Cited By ~ 1

Author(s):

Miao Zhang ◽

Lin Guo ◽

Long-Fei Lin ◽

Chang-Hai Qu ◽

Xing-Bin Yin ◽

...

Keyword(s):

Cell Line ◽

K562 Cell ◽

Computational Study ◽

Arsenic Concentration ◽

K562 Cells ◽

Cell Permeability ◽

K562 Cell Line ◽

Apparent Permeability ◽

Indigo Naturalis

Realgar and indigo naturalis are clinically combined to treat varieties of leukemia. Exploring the drug-drug interactions might be beneficial to find active substances and develop new targeted drugs. This study aimed at exploring the change of arsenic concentration in mice and across MDCK-MDR1 cells and the cytotoxicity on K562 cells when realgar and indigo naturalis were combined. In the presence or absence of indigo naturalis, pharmacokinetics and cell-based permeability assays were used to evaluate the change of arsenic concentration, and K562 cell line was applied to evaluate the change of cytotoxicity. The drug concentration-time profiles exhibited that the combination medication group generated higher AUC, thalf, and longer MRT for arsenic, compared with the single administration of realgar. The apparent permeability coefficients (Papp) of bidirectional transport in MDCK-MDR1 cell permeability experiments showed that arsenic permeability obviously went up when indigo naturalis was incubated together. The combination medication significantly decreased the cell viability of K562 cells when both the concentration of realgar and the concentration of indigo naturalis were nontoxic. The pharmacokinetic research, the MDCK-MDR1 based permeability study, and the K562 cytotoxicity study were united together to verify the combination medication of realgar and indigo naturalis enhanced the absorption and the permeability across cells for arsenic and effectively inhibited the proliferation of K562 cell line. The molecular binding of As4S4 and indirubin was analyzed by computational study. It is predicted that the formation of the complex [As4S4…Indirubin] involves noncovalent interaction that changes the concentration of arsenic.

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A nanocomplex of Cu(II) with theophylline drug; synthesis, characterization, and anticancer activity against K562 cell line

Journal of Molecular Structure ◽

10.1016/j.molstruc.2017.11.029 ◽

2018 ◽

Vol 1155 ◽

pp. 450-456 ◽

Cited By ~ 6

Author(s):

Maryam Sahlabadi ◽

Marzieh Daryanavard ◽

Hassan Hadadzadeh ◽

Zahra Amirghofran

Keyword(s):

Anticancer Activity ◽

Cell Line ◽

K562 Cell ◽

K562 Cell Line ◽

Drug Synthesis

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Inhibition of Glucose-6-Phosphate Dehydrogenase Could Enhance 1,4-Benzoquinone-Induced Oxidative Damage in K562 Cells

Oxidative Medicine and Cellular Longevity ◽

10.1155/2016/3912515 ◽

2016 ◽

Vol 2016 ◽

pp. 1-11 ◽

Cited By ~ 6

Author(s):

Juan Zhang ◽

Meng Cao ◽

Wenwen Yang ◽

Fengmei Sun ◽

Cheng Xu ◽

...

Keyword(s):

Oxidative Damage ◽

Cell Line ◽

K562 Cell ◽

K562 Cells ◽

Control Group ◽

K562 Cell Line ◽

G6pd Gene ◽

Oxidative Metabolites ◽

Chemical Contaminant ◽

Glucose 6 Phosphate Dehydrogenase

Benzene is a chemical contaminant widespread in industrial and living environments. The oxidative metabolites of benzene induce toxicity involving oxidative damage. Protecting cells and cell membranes from oxidative damage, glucose-6-phosphate dehydrogenase (G6PD) maintains the reduced state of glutathione (GSH). This study aims to investigate whether the downregulation of G6PD in K562 cell line can influence the oxidative toxicity induced by 1,4-benzoquinone (BQ). G6PD was inhibited in K562 cell line transfected with the specific siRNA of G6PD gene. An empty vector was transfected in the control group. Results revealed that G6PD was significantly upregulated in the control cells and in the cells with inhibited G6PD after they were exposed to BQ. The NADPH/NADP and GSH/GSSG ratio were significantly lower in the cells with inhibited G6PD than in the control cells at the same BQ concentration. The relative reactive oxygen species (ROS) level and DNA oxidative damage were significantly increased in the cell line with inhibited G6PD. The apoptotic rate and G2 phase arrest were also significantly higher in the cells with inhibited G6PD and exposed to BQ than in the control cells. Our results suggested that G6PD inhibition could reduce GSH activity and alleviate oxidative damage. G6PD deficiency is also a possible susceptible risk factor of benzene exposure.

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