Background: The non-immunosuppressive cyclosporine analog PSC 833 has been shown to reverse multidrug-resistance of neoplastic cells including the MDR-1 gene coded P-glycoprotein (P-gp)-mediated cells resistant to paclitaxel.
Materials And Methods: Apoptosis was demonstrated in drug-sensitive HL-60 and multidrug-resistant human promyelocytic leukemia HL-60/ADR (MRP) and HL-60/VCR (MDR-1) cells in vitro with the aid of flow cytometry, DNA analysis and western blotting.
Results: The techniques used herein determined accumulation of paclitaxel/PSC 833 induced apoptotic cells with sub-G0 (hypodiploid) DNA content and blocked in the G2/M phase of the cell cycle, internucleosomal DNA fragmentation, poly (ADP-ribose) polymerase cleavage, Bcl-2 modulation and Bax up-regulation, without any significant alterations in the levels of Bcl-xL, CD95/Fas or Fas-L proteins.
Conclusion: Drug resistance modulator PSC 833 abolished the P-gp-mediated multidrug-resistance to paclitaxel and paclitaxel-induced apoptosis in human myeloid leukemia (HL-60/VCR) cells in vitro. Furthermore, PSC 833 alone induced apoptosis in parental drug-sensitive leukemia cells, but not in both multidrug-resistant sublines studied.
Download full-text PDF |
Source |
|---|
Publication Analysis
Top Keywords
Similar Publications
Screening of photosensitizers-ATP binding cassette (ABC) transporter interactions .
Cancer Drug Resist
September 2024
Fischell Department of Bioengineering, University of Maryland, College Park, MD 20742, USA.
Article Synopsis
- This study explores how ATP-binding cassette (ABC) transporters reduce the effectiveness of cancer treatments by transporting seven clinically used photosensitizers out of cancer cells.* -
- The research involved human breast cancer cell lines to assess how specific transport proteins (P-gp, ABCG2, MRP1) affect the accumulation of these photosensitizers, with some inhibitors showing effectiveness in blocking transport.* -
- Key findings indicate that certain photosensitizers can be impacted by these transporters, leading to reduced efficacy in photodynamic therapy, while others, like temoporfin and talaporfin sodium, do not seem to be transported by ABCG2.*
Potency and mechanism of p-glycoprotein chemosensitizers in rainbow trout (Oncorhynchus mykiss) hepatocytes.
Fish Physiol Biochem
December 2024
Department of Biological Sciences, Simon Fraser University, 8888 University Drive Burnaby, British Columbia, Canada.
The membrane efflux transporter P-glycoprotein (P-gp, [ABCB1, MDR1]) exports a wide range of xenobiotic compounds, resulting in a continuous first line of defense against toxicant accumulation at basal expression levels, and contributing to the multixenobiotic resistance (MXR) phenotype at elevated expression levels. Relatively little information exists on P-gp inhibition in fish by chemosensitizers, compounds which lower toxicity thresholds for harmful P-gp substrates in complex mixtures. The effects of four known mammalian chemosensitizers (cyclosporin A [CsA], quinidine, valspodar [PSC833], and verapamil) on the P-gp-mediated transport of rhodamine 123 (R123) and cortisol in primary cultures of rainbow trout (Oncorhynchus mykiss) hepatocytes were examined.
View Article and Find Full Text PDFEffect of Apolipoprotein E isoforms on the Abundance and Function of P-glycoprotein in Human Brain Microvascular Endothelial Cells.
Pharm Res
July 2024
Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, Victoria, 3052, Australia.
Background: Individuals with Alzheimer's disease (AD) often require many medications; however, these medications are dosed using regimens recommended for individuals without AD. This is despite reduced abundance and function of P-glycoprotein (P-gp) at the blood-brain barrier (BBB) in AD, which can impact brain exposure of drugs. The fundamental mechanisms leading to reduced P-gp abundance in sporadic AD remain unknown; however, it is known that the apolipoprotein E (apoE) gene has the strongest genetic link to sporadic AD development, and apoE isoforms can differentially alter BBB function.
View Article and Find Full Text PDFAssessment of P-glycoprotein function using canine intestinal organoid-derived epithelial interfaces.
Xenobiotica
June 2024
Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, Washington, USA.
P-glycoprotein (P-gp), a multidrug efflux pump encoded by the (formerly ) gene, plays a crucial role in limiting drug absorption and eliminating toxic compounds in both humans and dogs. However, species-specific differences in P-gp substrates necessitate the development of canine-specific evaluation systems. Canine intestinal organoids derived monolayers offer a promising platform for studying drug transport, yet P-gp-mediated transport in these models remains unexplored.
View Article and Find Full Text PDFComparative study on ABCB1-dependent efflux of anthracyclines and their metabolites: consequences for cancer resistance.
Xenobiotica
December 2023
Department of Pharmaceutical Biochemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland.
1. ABCB1 (P-glycoprotein, MDR1) is one of the most important transporter involved in cancer multi-drug resistance. It also plays a significant role in cancer resistance against anthracyclines, an anticancer group of drugs, including doxorubicin and daunorubicin.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!