scholarly journals Differences in Substrate Specificity among Glutathione Conjugates (GS-X) Pump Family Members: Comparison between Multidrug Resistance-associated Protein and a Novel Transporter Expressed on a Cisplatin-resistant Cell Line (KCP-4)

1999 ◽  
Vol 90 (4) ◽  
pp. 439-447 ◽  
Author(s):  
Kaoru Ueda ◽  
Hiroshi Suzuki ◽  
Shin-ichi Akiyama ◽  
Yuichi Sugiyama
Keyword(s):  
Multidrug Resistance ◽  
Substrate Specificity ◽  
Cell Line ◽  
Family Members ◽  
Resistant Cell ◽  
Resistant Cell Line ◽  
Glutathione Conjugates

scholarly journals Multidrug resistance in tumour cells: characterisation of the multidrug resistant cell line K562-Lucena 1

2001 ◽  
Vol 73 (1) ◽  
pp. 57-69 ◽  
Author(s):  
VIVIAN M. RUMJANEK ◽  
GILMA S. TRINDADE ◽  
KAREN WAGNER-SOUZA ◽  
MICHELE C. MELETTI-DE-OLIVEIRA ◽  
LUIS F. MARQUES-SANTOS ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Cell Line ◽  
Anticancer Agents ◽  
Vinca Alkaloid ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Resistant Cell ◽  
Cross Reactivity ◽  
Resistant Cell Line ◽  
P Glycoprotein

Multidrug resistance to chemotherapy is a major obstacle in the treatment of cancer patients. The best characterised mechanism responsible for multidrug resistance involves the expression of the MDR-1 gene product, P-glycoprotein. However, the resistance process is multifactorial. Studies of multidrug resistance mechanisms have relied on the analysis of cancer cell lines that have been selected and present cross-reactivity to a broad range of anticancer agents. This work characterises a multidrug resistant cell line, originally selected for resistance to the Vinca alkaloid vincristine and derived from the human erythroleukaemia cell K562. This cell line, named Lucena 1, overexpresses P-glycoprotein and have its resistance reversed by the chemosensitisers verapamil, trifluoperazine and cyclosporins A, D and G. Furthermore, we demonstrated that methylene blue was capable of partially reversing the resistance in this cell line. On the contrary, the use of 5-fluorouracil increased the resistance of Lucena 1. In addition to chemotherapics, Lucena 1 cells were resistant to ultraviolet A radiation and hydrogen peroxide and failed to mobilise intracellular calcium when thapsigargin was used. Changes in the cytoskeleton of this cell line were also observed.

scholarly journals B4GALT1 gene knockdown inhibits the hedgehog pathway and reverses multidrug resistance in the human leukemia K562/adriamycin-resistant cell line

IUBMB Life ◽  
2012 ◽  
Vol 64 (11) ◽  
pp. 889-900 ◽  
Author(s):  
Huimin Zhou ◽  
Zhaohai Zhang ◽  
Chunqing Liu ◽  
Changgong Jin ◽  
Jianing Zhang ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Cell Line ◽  
Resistant Cell ◽  
Resistant Cell Line ◽  
Hedgehog Pathway ◽  
Gene Knockdown ◽  
Human Leukemia

Research of Synergetic Reversal in Adriamycin - Resistance by the Application of Magnetic Nanoparticle of Fe3O4 and Tetrandrine in K562/A02 Leukemic Cells.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4173-4173
Author(s):  
Bao-An Chen ◽  
Qian Shun ◽  
Xue-Mei Wang ◽  
Ren-Yu Zhang ◽  
Feng Gao ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Growth Inhibition ◽  
Cell Line ◽  
Fluorescence Intensity ◽  
Resistant Cell ◽  
Resistant Cell Line ◽  
Polymerization Process ◽  
Nano Composites ◽  
Mdr1 Mrna ◽  
Fe3o4 Mnps

Objective: To prepare functionalized Fe3O4-magnetic nanoparticles(Fe3O4-MNPs) loaded with adriamycin(ADM) or Fe3O4-MNPs co-polymerized with ADM and tetrandrine(Tet) to investigate whether the temperature, time or ratio of drug to nanoparticles influences the polymerization. To study the reversal role that the drug-loaded nano-composites play in K562 and one of its resistant cell line K562/A02 and to learn the reversal mechanism of this kind of treatments so as to provide theoretic evidence for the clinical application of them as resistance modifying agents. Method: The drug-loaded nanoparticles were prepared using mechanical absorption polymerization process in different condition of 4° or 37° for 24h or 48h. To investigate whether Fe3O4-MNPs loaded with ADM and Tet would play a synergetic reverse role in multidrug resistant cell, the drug-loaded nanoparticles by mechanical absorption polymerization were prepared to act with K562 and one of its resistant cell line K562/A02. The survival of cells which were cultured with drug-loaded nano-composites for 48h was observed through MTT assay, the growth inhibition efficacy of cells was calculated then. Using cells under the same condition described before, we took use of fluorescence microscope to measure fluorescence intensity of intracellular ADM at a wavelength of 488nm. P-glycoprotein (P-gp) was analyzed with flow cytometer. The expression of mdr1 mRNA was measured by RT-PCR. Results: The results showed that the growth inhibition efficacy of both the two cells increased with augmenting concentration of Fe3O4-MNPs which were loaded with drugs. The condition of 4° and 48h was significantly better than that of 37° and 24h respectively. Both Fe3O4-MNPs loaded with ADM or Fe3O4-MNPs co-polymerized with ADM and Tet elevated the intracellular ADM accumulation in K562/A02. However, no linear correlation was found between fluorescence intensity of intracellular adriamycin and augmenting concentration of Fe3O4-MNPs in K562/A02. Tet could downregulate the level of mdr-1 gene and decrease the expression of P-gp. Furthermore, Tet polymerized with Fe3O4-MNPs reinforced this downregulation, causing a 100-fold more decrease in mdr1 mRNA level, but did not reduce total P-gp content. Conclusions: Fe3O4-MNPs can load ADM or both ADM and Tet by mechanical absorption polymerization, which depends on proper temperature and time. Furthermore, the drug-loaded nano-composites have the ability in multidrug resistance reversal. Fe3O4-MNPs loaded with ADM or Tet can enhance the effective accumulation of the drugs in K562/A02 and Fe3O4-MNPs loaded with Tet obviously reverse multidrug resistance by reinforcing mdr1 gene downregulation. Functionalized Fe3O4-MNPs loaded with Tet probably have synergetic effect on reversal in multidrug resistance.

scholarly journals Genomic Adaption and Mutational Patterns in a HaCaT Subline Resistant to Alkylating Agents and Ionizing Radiation

2021 ◽  
Vol 22 (3) ◽  
pp. 1146
Author(s):  
Reinhard Ullmann ◽  
Benjamin Valentin Becker ◽  
Simone Rothmiller ◽  
Annette Schmidt ◽  
Horst Thiermann ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Line ◽  
Copy Number ◽  
Resistant Cell ◽  
Resistant Cell Line ◽  
Chromosomal Translocations ◽  
Dna Copy Number ◽  
Mutational Signatures ◽  
Copy Number Changes ◽  
And Oxidative Stress

Sulfur mustard (SM) is a chemical warfare agent that can damage DNA via alkylation and oxidative stress. Because of its genotoxicity, SM is cancerogenic and the progenitor of many chemotherapeutics. Previously, we developed an SM-resistant cell line via chronic exposure of the popular keratinocyte cell line HaCaT to increasing doses of SM over a period of 40 months. In this study, we compared the genomic landscape of the SM-resistant cell line HaCaT/SM to its sensitive parental line HaCaT in order to gain insights into genetic changes associated with continuous alkylation and oxidative stress. We established chromosome numbers by cytogenetics, analyzed DNA copy number changes by means of array Comparative Genomic Hybridization (array CGH), employed the genome-wide chromosome conformation capture technique Hi-C to detect chromosomal translocations, and derived mutational signatures by whole-genome sequencing. We observed that chronic SM exposure eliminated the initially prevailing hypotetraploid cell population in favor of a hyperdiploid one, which contrasts with previous observations that link polyploidization to increased tolerance and adaptability toward genotoxic stress. Furthermore, we observed an accumulation of chromosomal translocations, frequently flanked by DNA copy number changes, which indicates a high rate of DNA double-strand breaks and their misrepair. HaCaT/SM-specific single-nucleotide variants showed enrichment of C > A and T > A transversions and a lower rate of deaminated cytosines in the CpG dinucleotide context. Given the frequent use of HaCaT in toxicology, this study provides a valuable data source with respect to the original genotype of HaCaT and the mutational signatures associated with chronic alkylation and oxidative stress.

Platinum pyridinecarboxaldimine complexes containing boronate esters

2004 ◽  
Vol 82 (12) ◽  
pp. 1692-1699 ◽  
Author(s):  
Hanni A Darwish ◽  
Stephen J Scales ◽  
Jennifer L Horton ◽  
Liliya G Nikolcheva ◽  
Haiwen Zhang ◽  
...  
Keyword(s):  
Ovarian Carcinoma ◽  
Key Words ◽  
Cell Line ◽  
Platinum Complexes ◽  
Resistant Cell ◽  
Resistant Cell Line ◽  
Boronate Esters ◽  
Human Ovarian Carcinoma

Condensation of 2-pyridinecarboxaldehydes with 2-, 3-, and 4-H2NC6H4Bpin (pin = 1,2-O2C2Me4) gave the corresponding boron-containing pyridinecarboxaldimines (N–NBpin). Addition of these ligands to [PtCl2(coe)]2 (coe = cis-cyclooctene) gave complexes of the type cis-PtCl2(N–NBpin) in moderate yields. The platinum complexes have been examined for their potential cytotoxicities against OV2008 (human ovarian carcinoma) and the analogous cisplatin-resistant cell line C13. Key words: boronate esters, pyridinecarboxaldimines, cytotoxicity, platinum, boron.

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