Molecular Mechanism of Matrine from Sophora alopecuroides in the Reversing Effect of Multi-Anticancer Drug Resistance in K562/ADR Cells.

In this study, we evaluated the reversing effect of matrine, the principal alkaloid derived from Sophora alopecuroides, on chemoresistant leukemia K562/ADR cells. Matrine in a range of the nontoxic concentration was employed in the whole study. IC50s of cancer medicines were tested using WST-8 assay. Drug export and apoptotic rates were examined using flow cytometry. The mRNA and protein expressions were quantified by quantitative real-time PCR and western blotting, respectively. Our data indicated that matrine had potent reversal properties augmenting cytotoxicity of cancer medicines on K562/ADR cells as well as apoptotic rates induced by doxorubicin. Moreover, matrine inhibited drug-exporting activity and expression of ATP-binding cassette subfamily B member 1 (ABCB1) on both mRNA and protein levels. That might result from inhibited NF-kappa B activation, which also led to restored intrinsic apoptosis. These findings suggest that matrine in the nontoxic concentration can suppress ABCB1 drug transport and facilitate the intrinsic apoptosis pathway through the inhibiting effect on NF-kappa B and has the potential to become an efficient sensitizer for anticancer drug resistance. PMID: 31871929 [PubMed - in process]
Source: Biomed Res - Category: Research Authors: Tags: Biomed Res Int Source Type: research

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CONCLUSIONS Our results suggest that the novel EGFR TKI olmutinib enhances the sensitivity of ETS1-overexpressing leukemia cells to Dox. PMID: 32830792 [PubMed - in process]
Source: Medical Science Monitor - Category: Research Tags: Med Sci Monit Source Type: research
Background: The optimal choice of initial antibiotic therapy for patients with high-risk febrile neutropenia (FN) in children is unclear and varies by the institution on the basis of local antibiograms and epidemiology of specific pathogens. The authors evaluated the appropriateness of antibiotics for the empiric treatment of FN in pediatric patients with cancer in our institution on the basis of changes in the epidemiology of organisms isolated from blood cultures (BCx). Methods: The authors conducted a retrospective medical record review of pediatric patients who received any oncology care (including patients with c...
Source: Journal of Pediatric Hematology Oncology - Category: Hematology Tags: Online Articles: Original Articles Source Type: research
CONCLUSION: Our study suggests that the MDR1C1236T polymorphism appears to be associated with the risk of AML. Further studies, including a large sample size, are needed to confirm these findings. PMID: 32711413 [PubMed - in process]
Source: Asian Pacific Journal of Cancer Prevention - Category: Cancer & Oncology Tags: Asian Pac J Cancer Prev Source Type: research
New Brunswick, N.J. (July 16, 2020) – Johnson &Johnson (NYSE: JNJ) today announced results for second-quarter 2020. “Our second quarter results reflect the impact of COVID-19 and the enduring strength of our Pharmaceutical business, where we saw continued growth even in this environment,” said Alex Gorsky, Chairman and Chief Executive Officer. “Thanks to the tireless work of our colleagues around the world and our broad range of capabilities, we continue to successfully navigate the external landscape, and we remain focused on advancing the development of a vaccine to help address this pandemic ...
Source: Johnson and Johnson - Category: Pharmaceuticals Source Type: news
a M. N. Abdelhafez A new series of methyl 2-(2-(4′-[2.2]paracyclophanyl)-hydrazinylidene)-3-substituted-4-oxothiazolidin-5-ylidene)acetates 3a–f were synthesized from the reaction of paracyclophanyl-acylthiosemicarbazides 2a–f with dimethyl acetylenedicarboxylate. Based upon nuclear magnetic resonance (NMR), infrared (IR), and mass spectra (HRMS), the structure of the obtained products was elucidated. X-ray structure analysis was also used as unambiguous tool to elucidate the structure of the products. The target compounds 3a–f were screened against 60 cancer cell lines. They dis...
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research
In this study, we investigated the modulatory potential of the CDK4/6 inhibitors abemaciclib, palbociclib, and ribociclib on AML resistance using peripheral blood mononuclear cells (PBMC) isolated from patients with de novo diagnosed AML. We first confirmed inhibitory effect of the tested drugs on ABCB1 and ABCG2 in ABC transporter-expressing resistant HL-60 cells while also showing the ability to sensitize the cells to cytotoxic drugs even as no effect on AML-relevant CRE isoforms was observed. All tested CDK4/6 inhibitors elevated mitoxantrone accumulations in CD34+ PBMC and enhanced accumulation of mitoxantrone was foun...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Abstract Conflicts with the notion that specific substrate interactions were required in the control of reaction path in active transport systems, P-glycoprotein showed extraordinarily low specificity. Therefore, overexpression P-glycoprotein excluded a large number of anticancer agents from cancer cells, and multidrug resistance happened. Several kinds of bisbenzylisoqunoline alkaloids were reported to modulate P-glycoprotein function and reverse drug resistance. In order to provide more information for their structure activity relationship on P-glycoprotein function, the effects of tetrandrine, isotetrandrine, f...
Source: Bioorganic and Medicinal Chemistry - Category: Chemistry Authors: Tags: Bioorg Med Chem Source Type: research
Multidrug resistance (MDR) in cancer arises from cross-resistance to structurally- and functionally-divergent chemotherapeutic drugs. In particular, MDR is characterized by increased expression and activity of ATP-binding cassette (ABC) superfamily transporters. Sphingolipids are substrates of ABC proteins in cell signaling, membrane biosynthesis, and inflammation, for example, and their products can favor cancer progression. Glucosylceramide (GlcCer) is a ubiquitous glycosphingolipid (GSL) generated by glucosylceramide synthase, a key regulatory enzyme encoded by the UDP-glucose ceramide glucosyltransferase (UGCG) gene. S...
Source: Journal of Biological Chemistry - Category: Chemistry Authors: Tags: Glycobiology and Extracellular Matrices Source Type: research
In this study, the polymeric micelles of benzoylated methoxy-poly (ethylene glycol)-b-oligo(ε-caprolactone) or mPEG-b-OCL-Bz loading with the flavonoids were prepared to solve these problems. The flavonoid-loaded micelles showed an average size of 13-20 nm and maximum loading capacity of 35% (w/w). The release of QCT (21%, 3 h) was lower than that of QTR (51%, 3 h) and RUT (58%, 3 h). QCT (free and micelle forms) exhibited significantly higher cytotoxicity against P-glycoprotein-overexpressing leukemia (K562/ADR) cells than QTR and RUT (p 
Source: AAPS PharmSciTech - Category: Drugs & Pharmacology Authors: Tags: AAPS PharmSciTech Source Type: research
Abstract Multidrug resistance (MDR) constitutes the major cause of the failure in anticancer therapy. One of the most important mechanisms leading to the occurrence of MDR is related to the modulation of cellular death pathways. The aim of this study was to determine the effect of quercetin (Q) on triggering the programed death of human promyelocytic leukemia sensitive cells HL60 as well as multidrug resistant HL60/VINC cells overexpressing P-glycoprotein and HL60/MX2 cells characterized by the presence of mutated α isoform of topoisomerase II and the absence of β isoform of this enzyme. Q exerted compa...
Source: Nutrition and Cancer - Category: Cancer & Oncology Authors: Tags: Nutr Cancer Source Type: research
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