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Objective: We examined the anti-tumor effect of pyrrolidinedithiocarbamate (PDTC) on HTLV-1-infected T clones and the mechanism of HTLV-1 Tax protein inhibition of PDTC-induced apoptosis.
Materials And Methods: Tax-nonproducing clones S1T and Su9T01, Tax-producing clones K3T and F6T, and Tax cDNA stably transfected S1TcTax clones S1TcTax04 and S1TcTax05 were examined for PDTC inhibition of thymidine incorporation and apoptosis induction by ISEL method. In addition, S1TcTax clones were analyzed by DNA histography and DNA fragmentation and also examined for p53, p21, or Bax protein expression by Western blot.
Results: PDTC inhibited thymidine incorporation of all four HTLV-1-infected T cells in a similar dose-dependent manner, but K3T and F6T were more resistant than S1T and Su9T01 in apoptosis induction. S1TcTax clones also showed resistance to PDTC-induced apoptosis as compared to Tax-nonproducing S1T and S1Tneo. DNA histography demonstrated that PDTC induces G1 arrest and apoptosis in S1T and S1Tneo, and that S1TcTax clones are also sensitive to PDTC in G1 arrest but resistant in apoptosis induction. DNA fragmentation also demonstrated ladder formation only in S1Tneo but not in S1TcTax04. Western blots demonstrated higher expression of p53 and p21 proteins in S1Tneo than in S1TcTax04 during whole phase after PDTC stimulation with moderate enhancement in S1Tneo but small in S1TcTax04. Bax protein expression was detected only at early phase in S1Tneo but was not detected in S1TcTax04.
Conclusion: These findings suggest that PDTC-induced apoptosis is related with Bax, and that G1 arrest is possibly related with p21. Tax might inhibit apoptosis induction mainly via inhibition of Bax expression preceded at least in part by p53 inhibition.
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http://dx.doi.org/10.1016/j.exphem.2003.11.008 | DOI Listing |
Mol Cell Biochem
December 2024
Henan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, Henan Xinxiang, 453003, People's Republic of China.
To investigate the promoting effect of extracellular vesicles derived from myocardial cells (CM-EVs) on the reprogramming of cardiac fibroblasts (CFs) into cardiomyocyte-like cells (iCMs) and their therapeutic effect on myocardial infarction (MI) in rats. Cell experiments: The differential adhesion method was used to obtain Sprague Dawley (SD) suckling rat CFs and cardiomyocytes (CMs), while the ultracentrifugation method was used to obtain CM-EVs. Transmission electron microscopy and nanoparticle tracking technology were used to analyze and determine the morphology and particle size of CM-EVs.
View Article and Find Full Text PDFCell Mol Life Sci
December 2024
Shanghai Key Laboratory of Biliary Tract Disease Research, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.
Background: Glioblastoma (GB) is the stage IV of glioma and mesenchymal GB represents the most common and malignant subtype characterized with elevated expression of a mesenchymal marker YKL-40 and resistance to immune drug therapy. Here, we determined if YKL-40 regulates kynurenine (Kyn) pathway (KP) metabolism that contributes to establishing an immune suppressive microenvironment in GB.
Methods: Tumor cells expressing YKL-40 from GB patients were isolated and activated cellular metabolisms were identified via gene microarray analysis.
Drug Dev Res
February 2025
Pharmaceutical Medicinal Chemistry and Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City, Cairo, Egypt.
New phthalazine-derived inhibitors for VEGFR-2 were synthesized for anticancer evaluations. Also, docking studies were performed to explore the suggested binding orientations of the novel derivatives inside the binding site of VEGFR-2. The achieved biological data were extremely interrelated to that of docking study.
View Article and Find Full Text PDFJ Biochem Mol Toxicol
January 2025
Department of Translational Medicine, Clinical Research Centre, Skåne University Hospital, Lund University, Malmö, Sweden.
Berberine, an isoquinoline alkaloid derived from various medicinal plants, emerges as a potential therapeutic agent against diverse human diseases. It has particularly shown notable anticancer efficacy against breast, colorectal, lung, prostate, and liver cancer. Berberine results in inhibition of cancer cell proliferation, induction of apoptosis, and suppressing angiogenesis, positioning it as a versatile, multitargeted therapeutic tool against cancer.
View Article and Find Full Text PDFEnviron Pollut
December 2024
Université de Lorraine, LIEC, CNRS, F-57000, Metz, France. Electronic address:
Lithium (Li) has become essential for energy and digital transitions, especially as a component of rechargeable batteries. Its growing uses worldwide lead to increasing anthropogenic releases of Li into the environment, which is making Li as an emerging contaminant. It is thus critical to evaluate the ecotoxicological impact of Li, which has been poorly studied unlike its human toxicology.
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