Multidrug resistance (MDR) to chemotherapeutic agents is a major obstacle to curative treatment of cancer. In various types of cancers, overexpression of glucosylceramide synthase (GCS) has been observed to be associated with MDR, thus making GCS a target for reversal of resistance. Our previous work demonstrated that GCS and Bcl-2 are co-overexpressed in the K562/A02 leukemia multidrug-resistant cell line compared with its sensitive counterpart, K562. In the present study, we investigated the effects of GCS on apoptosis in K562/A02 and the associated molecular mechanisms. Our results indicate that the inhibition of GCS caused downregulation of Bcl-2 as well as apoptosis enhancement in response to ADM via the ERK pathway, while JNK or p38 MAPK signaling appeared to play less significant roles in the regulation of apoptosis and MDR in K562/A02 cells. Targeting GCS by siRNA also enhanced ceramide accumulation, which is involved in GCS knockdown-induced inhibition of ERK activation and Bcl-2 expression levels.
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http://dx.doi.org/10.1007/s12185-014-1679-7 | DOI Listing |
mBio
January 2025
Division of Infectious Diseases, Boston Children's Hospital, Boston, Massachusetts, USA.
Unlabelled: Streptolysin O (SLO) is a virulence determinant of group A (), the agent of streptococcal sore throat and severe invasive infections. SLO is a member of a family of bacterial pore-forming toxins known as cholesterol-dependent cytolysins, which require cell membrane cholesterol for pore formation. While cholesterol is essential for cytolytic activity, accumulating data suggest that cell surface glycans may also participate in the binding of SLO and other cholesterol-dependent cytolysins to host cells.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Lipid Pathobiochemistry Group, German Cancer Research Center, Im Neuenheimer Feld 581, 69120 Heidelberg, Germany.
Hepatocellular carcinoma () is one of the leading causes of cancer deaths due to its late diagnosis and restricted therapeutic options. Therefore, the search for appropriate alternatives to commonly applied therapies remains an area of high clinical need. Here we investigated the therapeutic potential of the glucosylceramide synthase (GCS) inhibitor Genz-123346 and the cationic amphiphilic drug aripiprazole on the inhibition of Huh7 and Hepa 1-6 hepatocellular cancer cell and tumor microsphere growth.
View Article and Find Full Text PDFInt J Biol Macromol
January 2025
School of Food and Bioengineering, Henan University of Animal Husbandry and Economy, Zhengzhou, Henan Province, People's Republic of China, Zhengzhou 450046, China. Electronic address:
Glucosylceramide synthase (UGCG) is a key enzyme that catalyzes the initial glycosylation step in the biosynthesis of glycosphingolipids (GSLs) derived from glucosylceramide. UGCG is closely associated with various cellular processes, including the cell cycle, angiogenesis, multidrug resistance, and pathogen invasion. In this study, a short hairpin RNA (shRNA) library designed to target key genes involved in the sphingolipid metabolic pathway was utilized to elucidate their roles in Pseudorabies Virus (PRV).
View Article and Find Full Text PDFPest Manag Sci
December 2024
Key Laboratory for Botanical Pesticide R&D of Shaanxi Province, Institute of Pesticide Science, Northwest A&F University, Yangling, P. R. China.
Background: The potential application of vanillin as a fungicide has garnered significant attention in the agricultural product market and food industries. Consequently, a novel series of vanillin derivatives containing thiazole and hydrazone fragments were strategically designed, synthesized, and evaluated for their antifungal activity against six representative plant phytopathogenic fungi.
Results: In the in vitro antifungal assay, some title vanillin derivatives showed good antifungal activity against Botrytis cinerea, Fusarium solani, and Magnaporthe grisea.
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