AI Article Synopsis
- Ceramide plays a crucial role in regulating programmed cell death (apoptosis) in leukemia, and Glucosylceramide synthase (GCS) helps cancer cells evade this process by converting ceramide into glucosylceramide.
- A study examined the expression levels of GCS in both clinical leukemia samples and cell lines, finding a strong correlation between high GCS levels and multidrug resistance in leukemia cells.
- The use of a GCS inhibitor, PPMP, demonstrated that blocking GCS increases the sensitivity of resistant leukemia cells to chemotherapy drugs like adriamycin, highlighting the potential of targeting GCS to overcome drug resistance in leukemia treatment.
Article Abstract
Ceramide, as a second messenger, initiates one of the major signal transduction pathways in tumor apoptosis. Glucosylceramide synthase (GCS) catalyzes glycosylation of ceramide and produces glucosylceramide. Through GCS, ceramide glycosylation allows cellular escape from ceramide-induced programmed cell death. Here we investigated the expression of GCS in human leukemia cells and an association between GCS and multidrug resistance of leukemia cells. Using RT-PCR technique the level of GCS gene was detected in 65 clinical multidrug resistance/non-resistance cases with leukemia, and in K562 and K562/A02 cell lines. AlamarBlue Assay was applied to confirm the multidrug resistant of K562/A02 cells. PPMP, which is a chemical inhibitor for GCS, was used to determine the relationship between GCS and drug-resistance in K562/A02 cells. In addition, multidrug resistance gene (mdr1), Bcl-2 and Bax mRNA was also analyzed by RT-PCR. The expression of GCS and mdr1 mRNA in clinic multidrug resistance samples exhibited significantly increased compared with clinic drug sensitive group (P<0.05). There was the positive correlation both the expression of GCS and mdr1 genes in leukemia samples (P<0.01, gamma=0.7). AlamarBlue Assay showed that the K562/A02 cell line was 115-fold more resistant to adriamycin and 36-fold more resistant to vincristine compared with drug-sensitive K562 cell line. There also was significant expression difference of GCS and mdr1 genes between K562 and K562/A02 cells. Bcl-2 gene exhibited higher expressions whatever in clinic drug-resistance samples or K562/A02 cells, whereas the expressions of Bax gene were higher in drug-sensitive samples and K562 cells. PPMP increased sensitivity to adriamycin toxicity by inhibiting GCS in K562/A02 cells. Therefore, it is suggested that a high level of GCS in leukemia is possible contributed to multidrug resistance of leukemia cells. Abnormally expressions of the genes in associated with cell apoptosis might be one of the main molecular pathology mechanisms of multidrug resistance caused by GCS gene.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.leukres.2007.07.006 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
AIE-Active Antibacterial Photosensitizer Disrupting Bacterial Structure: Multicenter Validation against Drug-Resistant Pathogens.
Small Methods
January 2025
Department of Laboratory Medicine, Guangdong Provincial Key Laboratory of Precision Medical Diagnostics, Guangdong Engineering and Technology Research Center for Rapid Diagnostic Biosensors, Guangdong Provincial Key Laboratory of Single Cell Technology and Application, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, P. R. China.
Antimicrobial resistance (AMR) has emerged as a global challenge in treating bacterial infections, creating an urgent need for broad-spectrum antimicrobial agents that can effectively combat multidrug-resistant (MDR) bacteria. Despite advancements in novel antimicrobial agents, many fail to comprehensively cover common resistant bacterial strains or undergo rigorous multi-center validation. Herein, a cationic AIE-active photosensitizers are developed, ITPM, derived from a triphenylamine-pyridine backbone to address the MDR challenge.
View Article and Find Full Text PDFClinical and microbiological characteristics and prognosis of invasive infection caused by in the community.
Ann Med
December 2025
Critical care department, Zhongshan City People's Hospital, Guangdong Province, China.
Background: The incidence of invasive infection of (Kp) in the community is increasing every year, and the high disability and mortality rates associated with them pose great challenges in clinical practice. This study aimed to explore the clinical and microbiological characteristics of Kp invasive infection in the community.
Method: This study investigated the data of 291 patients with Kp infection in the community in three hospitals (Zhongshan City, Guangdong Province) from January 2020 to August 2023.
Doxycycline Restores Gemcitabine Sensitivity in Preclinical Models of Multidrug-Resistant Intrahepatic Cholangiocarcinoma.
Cancers (Basel)
January 2025
Candiolo Cancer Institute, FPO-IRCCS, 10060 Candiolo, Italy.
Background/objectives: Intrahepatic cholangiocarcinoma (iCCA) is a malignant liver tumor with a rising global incidence and poor prognosis, largely due to late-stage diagnosis and limited effective treatment options. Standard chemotherapy regimens, including cisplatin and gemcitabine, often fail because of the development of multidrug resistance (MDR), leaving patients with few alternative therapies. Doxycycline, a tetracycline antibiotic, has demonstrated antitumor effects across various cancers, influencing cancer cell viability, apoptosis, and stemness.
View Article and Find Full Text PDFChemical Profile and Antibacterial Activity of L. cv Graciano Pomace Extracts Obtained by Green Supercritical CO Extraction Method Against Multidrug-Resistant Strains.
Foods
December 2024
Instituto de Ciencias de la Vid y del Vino (ICVV) (Universidad de La Rioja, Consejo Superior de Investigaciones Científicas (CSIC), Gobierno de La Rioja), 26007 Logroño, Spain.
The objectives of this study were to obtain and characterise polyphenolic extracts from red grape pomace of L. cv Graciano via conventional solvent extraction (SE) and green supercritical fluid extraction (SFE) and to evaluate their antibacterial activity against susceptible and multidrug-resistant strains of intestinal origin. The SE and SFE methods were optimised, and ultra-performance liquid chromatography/mass spectrometry (UPLC/QqQ-MS/MS) analysis revealed 38 phenolic compounds in the SE sample, with anthocyanins being the predominant polyphenols, and 21 phenolic compounds in the SFE samples, among which hydroxybenzoic acids and flavonols were the predominant compounds.
View Article and Find Full Text PDFStudy on the Chemical Composition and Multidrug Resistance Reversal Activity of (Euphorbiaceae).
Int J Mol Sci
January 2025
Key Laboratory of Xinjiang Phytomedicine Resource and Uilization, Ministry of Education, Shihezi 832002, China.
belongs to the family Euphorbiaceae and is widely distributed in northern Xinjiang, making it a characteristic plant of the region in Xinjiang, China. The chemical composition and biological activity of have not yet been reported, although certain compounds isolated from plants in Xinjiang, China, have demonstrated exceptional multidrug resistance (MDR) reversal. This study aims to investigate the chemical components present in with the potential to reverse MDR.
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!