scholarly journals YQ36: A Novel Bisindolylmaleimide Analogue Induces KB/VCR Cell Death

2009 ◽  
Vol 2009 ◽  
pp. 1-11
Author(s):  
Ji Cao ◽  
Lei Zhang ◽  
Qing Ye ◽  
Xinglu Zhou ◽  
Jianshu Lou ◽  
...  
Keyword(s):  
Dna Damage ◽  
Multidrug Resistance ◽  
Cell Lines ◽  
Parental Cell ◽  
Mitochondrial Pathway ◽  
Chemotherapeutic Agents ◽  
Multidrug Resistance Proteins ◽  
Glycoprotein P ◽  
Resistance Proteins ◽  
P Glycoprotein

Overexpression of multidrug resistance proteins P-glycoprotein (P-gp, MDR1) causes resistance of the tumor cells against a variety of chemotherapeutic agents. 3-(1-methyl-1H-indol-3-yl)-1-phenyl-4-(1-(3-(piperidin-1-yl)propyl)-1H-pyrazolo[3,4-b]pyridine-3-yl)-1H-pyrrole-2,5-dione (YQ36) is a novel analogue of bisindolylmaleimide, which has been reported to overcome multidrug resistance. Here, we dedicated to investigate the anticancer activity of YQ36 on KB/VCR cells. The results revealed that YQ36 exhibited great antiproliferative activity on three parental cell lines and MDR1 overexpressed cell lines. Moreover, the hypersensitivity of YQ36 was confirmed on the base of great apoptosis induction and unaltered intracellular drug accumulation in KB/VCR cells. Further results suggested that YQ36 could not be considered as a substrate of P-gp, which contributed to its successfully escaping from the efflux mediated by P-gp. Interestingly, we observed that YQ36 could accumulate in nucleus and induce DNA damage. YQ36 could also induce the activation of caspase-3, imposing effects on the mitochondrial function. Collectively, our data demonstrated that YQ36 exhibited potent activities against MDR cells, inducing DNA damage and triggering subsequent apoptosis via mitochondrial pathway.

Characterization of P-glycoprotein and multidrug resistance proteins in rat kidney and intestinal cell lines

2007 ◽  
Vol 30 (1) ◽  
pp. 36-44 ◽  
Author(s):  
Femke M. van de Water ◽  
Johanna M. Boleij ◽  
Janny G.P. Peters ◽  
Frans G.M. Russel ◽  
Rosalinde Masereeuw
Keyword(s):  
Multidrug Resistance ◽  
Cell Lines ◽  
Rat Kidney ◽  
Intestinal Cell ◽  
Multidrug Resistance Proteins ◽  
Resistance Proteins ◽  
P Glycoprotein ◽  
Intestinal Cell Lines

Imatinib Is a Substrate for Various Multidrug Resistance Proteins

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4249-4249
Author(s):  
Krzysztof Czyzewski ◽  
Jan Styczynski
Keyword(s):  
Multidrug Resistance ◽  
Chronic Myeloid Leukemia ◽  
Cell Line ◽  
Cell Lines ◽  
Myeloid Leukemia ◽  
Resistant Cell ◽  
Multidrug Resistance Proteins ◽  
Resistance Proteins ◽  
Imatinib Resistant ◽  
Ic50 Value

Abstract An increasing resistance to imatinib is an emerging problem in patients with chronic myeloid leukemia. The aim of the study was assessing possible mechanisms of cellular drug resistance in imatinib-resistant derivates of chronic myeloid leukemia K-562 cell line. A parental K-562 and its imatinib-resistant derivate cell lines were used. Cell lines were tested for cytotoxicity of imatinib, cytarabine, busulfan and etoposide. Multidrug resistance proteins expression, rhodamine retention and daunorubicin accumulation were measured for each cell line. Imatinib was cytotoxic to all tested groups of cells. Exposition of K-562 cell line to low concentrations of imatinib caused an increase of IC50 value of imatinib, while exposition of K-562 cell line to higher concentrations of imatinib decreased IC50 value of imatinib. There was a high correlation between PGP, MRP1 and LRP expression and IC50 for imatinib and etoposide. All tested cell lines were highly resistant to cytarabine. Rhodamine retention alone and in the presence of cyclosporine was the lowest in imatinib-resistant K-562R-0.1 cell line, what suggest high PGP activity in this cell line. Daunorubicin accumulation was the highest in parental K-562 cell line and it decreased in imatinib-resistant cell lines, which were characterized by high PGP, MRP1 and LRP expression. These data suggest that imatinib is a substrate for multidrug resistance proteins, and an increased expression of PGP, MRP1 and LRP play a role in resistance to imatinib in chronic myeloid leukemia.

scholarly journals Multidrug resistance P-glycoprotein monoclonal antibody JSB-1 crossreacts with pyruvate carboxylase.

1995 ◽  
Vol 43 (12) ◽  
pp. 1187-1192 ◽  
Author(s):  
V V Rao ◽  
D C Anthony ◽  
D Piwnica-Worms
Keyword(s):  
Monoclonal Antibody ◽  
Multidrug Resistance ◽  
Pyruvate Carboxylase ◽  
Peptide Mapping ◽  
Bovine Liver ◽  
Cross Reactivity ◽  
Chemotherapeutic Agents ◽  
Glycoprotein P ◽  
Mitochondrial Inner Membrane ◽  
P Glycoprotein

Multidrug resistance (MDR) is associated with overexpression of a 170 KD plasma membrane P-glycoprotein (P-gp), a putative energy-dependent efflux transporter that reduces intracellular accumulation of chemotherapeutic agents. For detection of P-gp expression in normal and malignant tissues, an MDR1-specific monoclonal antibody (MAb) JSB-1 has been used extensively. In this report we show that MAb JSB-1 crossreacts with a protein of M(r) approximately 130,000 present in rat liver mitochondrial inner membrane/matrix fractions. Peptide mapping and microsequencing identify this protein as pyruvate carboxylase (PC), an abundant mitochondrial enzyme. MAb JSB-1 also crossreacts with purified PC from bovine liver. Under immunoblotting conditions, this crossreactivity is partially abolished by pre-incubation of MAb JSB-1 with a 1000-fold molar excess of MAb C494 epitope-specific peptide (PNTLEGN), indicating that the epitope of MAb JSB-1 may either overlap with or be in close proximity to that of MAb C494. Immunohistochemical cross-reactivity was also demonstrated in cryosections of human skeletal muscle, a tissue known not to express P-gp. MAb JSB-1 strongly immunostained Type 1 fibers, the subtype known to contain abundant mitochondria. Use of MAb JSB-1 for detection of MDR1 P-gp expression should be approached with caution.

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