The activity of latent benzoperimidine esters to inhibit P-glycoprotein and multidrug resistance-associated protein 1 dependent efflux of pirarubicin from several lines of multidrug resistant tumor cells

2004 ◽  
Vol 28 (4) ◽  
pp. 283-293 ◽  
Author(s):  
Dorota Głowacka-Rogacka ◽  
Małgorzata Arciemiuk ◽  
Agnieszka Kupiec ◽  
Maria M. Bontemps-Gracz ◽  
Edward Borowski ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Tumor Cells ◽  
Multidrug Resistant ◽  
P Glycoprotein

scholarly journals Overcoming multidrug-resistance in vitro and in vivo using the novel P-glycoprotein inhibitor 1416

2012 ◽  
Vol 32 (6) ◽  
pp. 559-566 ◽  
Author(s):  
Yan Xu ◽  
Feng Zhi ◽  
Guangming Xu ◽  
Xiaolei Tang ◽  
Sheng Lu ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Cancer Chemotherapy ◽  
Antitumour Activity ◽  
Multidrug Resistant ◽  
The Novel ◽  
Mice Model ◽  
P Glycoprotein ◽  
Channel Currents

MDR (multidrug-resistance) represents a major obstacle to successful cancer chemotherapy and is usually accomplished by overexpression of P-gp (P-glycoprotein). Much effort has been devoted to developing P-gp inhibitors to modulate MDR. However, none of the inhibitors on the market have been successful. 1416 [1-(2,6-dimethylphenoxy)-2-(3,4-dimethoxyphenylethylamino)propane hydrochloride (phenoprolamine hydrochloride)] is a new VER (verapamil) analogue with a higher IC50 for blocking calcium channel currents than VER. In the present paper, we examined the inhibition effect of 1416 on P-gp both in vitro and in vivo. 1416 significantly enhanced cytotoxicity of VBL (vinblastine) in P-gp-overexpressed human multidrug-resistant K562/ADM (adriamycin) and KBV cells, but had no such effect on the parent K562 and KB cells. The MDR-modulating function of 1416 was further confirmed by increasing intracellular Rh123 (rhodanmine123) content in MDR cells. Human K562/ADM xenograft-nude mice model verified that 1416 potentiates the antitumour activity of VBL in vivo. RT-PCR (reverse transcriptase-PCR) and FACS analysis demonstrated that the expression of MDR1/P-gp was not affected by 1416 treatment. All these observations suggest that 1416 could be a promising agent for overcoming MDR in cancer chemotherapy.

scholarly journals The Fluorescent Probe Bodipy-FL-Verapamil Is a Substrate for Both P-glycoprotein and Multidrug Resistance-related Protein (MRP)-1

2002 ◽  
Vol 50 (5) ◽  
pp. 731-734 ◽  
Author(s):  
Enrico Crivellato ◽  
Luigi Candussio ◽  
Anna M. Rosati ◽  
Fiora Bartoli-Klugmann ◽  
Franco Mallardi ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Drug Transport ◽  
Mrna Level ◽  
Fluorescent Microscopy ◽  
Flow Cytometric Analysis ◽  
Cell Types ◽  
Multidrug Resistant ◽  
Related Protein ◽  
P Glycoprotein ◽  
Multidrug Resistance Related Protein

Several fluorescent probes have been used in functional studies to analyze drug transport in multidrug-resistant cells by fluorescent microscopy. Because many of these molecules have some drawbacks, such as toxicity, nonspecific background, or accumulation in mitochondria, new fluorescent compounds have been proposed as more useful tools. Among these substances, Bodipy-FL-Verapamil, a fluorescent conjugate of the drug efflux blocker verapamil, has been used to study P-glycoprotein activity in different cell types. In this study we tested by fluorescent microscopy the accumulation of Bodipy-FL- Verapamil in cell lines that overexpress either P-glycoprotein (P-gp) or multidrug resistance-related protein 1 (MRP1). Expression of P-gp and MRP1 was evaluated at the mRNA level by RT-PCR technique and at the protein level by flow cytometric analysis using C219 and MRP-m6 monoclonal antibodies. Results indicate that Bodipy-FL-Verapamil is actually a substrate for both proteins. As a consequence, any conclusion about P-gp activity obtained by the use of Bodipy-FL-Verapamil as fluorescent tracer should be interpreted with caution.

Expression of hamster P-glycoprotein and multidrug resistance in DNA-mediated transformants of mouse LTA cells

1987 ◽  
Vol 7 (2) ◽  
pp. 718-724
Author(s):  
K L Deuchars ◽  
R P Du ◽  
M Naik ◽  
D Evernden-Porelle ◽  
N Kartner ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Dna Sequences ◽  
Multidrug Resistant ◽  
Cross Resistance ◽  
Recipient Mouse ◽  
Strongly Correlated ◽  
Wild Type ◽  
Glycoprotein P ◽  
Single Drug ◽  
P Glycoprotein

The overexpression of a plasma membrane glycoprotein, P-glycoprotein, is strongly correlated with the expression of multidrug resistance. This phenotype (frequently observed in cell lines selected for resistance to a single drug) is characterized by cross resistance to many drugs, some of which are used in cancer chemotherapy. In the present study we showed that DNA-mediated transformants of mouse LTA cells with DNA from multidrug-resistant hamster cells acquired the multidrug resistance phenotype, that the transformants contained hamster P-glycoprotein DNA sequences, that these sequences were amplified whereas the recipient mouse P-glycoprotein sequences remained at wild-type levels, and that the overexpressed P-glycoprotein in these cells was of hamster origin. Furthermore, we showed that the hamster P-glycoprotein sequences were transfected independently of a group of genes that were originally coamplified and linked within a 1-megabase-pair region in the donor hamster genome. These data indicate that the high expression of P-glycoprotein is the only alteration required to mediate multidrug resistance.

scholarly journals Intercellular transfer of P-glycoprotein mediates acquired multidrug resistance in tumor cells

2005 ◽  
Vol 102 (6) ◽  
pp. 1933-1938 ◽  
Author(s):  
A. Levchenko ◽  
B. M. Mehta ◽  
X. Niu ◽  
G. Kang ◽  
L. Villafania ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Tumor Cells ◽  
Intercellular Transfer ◽  
P Glycoprotein

scholarly journals Reversal of Multidrug Resistance by 7-O-Benzoylpyripyropene A in Multidrug-Resistant Tumor Cells.

2000 ◽  
Vol 53 (10) ◽  
pp. 1201-1206 ◽  
Author(s):  
MUN-CHUAL RHO ◽  
MASAHIKO HAYASHI ◽  
AKIKO FUKAMI ◽  
RIKA OBATA ◽  
TOSHIAKI SUNAZUKA ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Tumor Cells ◽  
Multidrug Resistant

scholarly journals Monoclonal Anti-P-glycoprotein Antibody-dependent Killing of Multidrug-resistant Tumor Cells by Human Mononuclear Cells

1990 ◽  
Vol 81 (11) ◽  
pp. 1155-1161 ◽  
Author(s):  
Yuji Heike ◽  
Hirofumi Hamada ◽  
Noriaki Inamura ◽  
Saburo Sone ◽  
Takeshi Ogura ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Mononuclear Cells ◽  
Multidrug Resistant ◽  
Human Mononuclear Cells ◽  
P Glycoprotein

Novel modulators to overcome P-glycoprotein-mediated multidrug resistance in tumor cells

2004 ◽  
Vol 42 (11) ◽  
pp. 644-645 ◽  
Author(s):  
H. Müller ◽  
W. Klinkhammer ◽  
M.U. Kassack ◽  
N. Eckstein ◽  
M. Wiese
Keyword(s):  
Multidrug Resistance ◽  
Tumor Cells ◽  
P Glycoprotein
Sign in / Sign up

Export Citation Format

Share Document