We examined the apoptotic response of two glioblastoma cells, p53 wild type U87 and p53 mutated T98G, to doxorubicin, bortezomib, and vorinostat, which respectively target DNA, 26S proteasome and histone deacetylase, to clarify p53's function in apoptosis. We demonstrated that doxorubicin induced apoptosis in U87 cells but not in T98G cells. The level of p53 was definitively correlated to the extent of DNA damage and apoptosis initiation. Dominant-negative p53 reduced p21 expression, but did not affect doxorubicin-induced apoptosis, so the transcriptional activity of p53 seemed not to participate in doxorubicin-induced apoptosis. However, p53 concentrated into the nucleus during heavy apoptosis. Bortezomib could induce apoptosis in U87 with high sensitivity and T98G cells with low sensitivity. In contrast, vorinostat promoted apoptosis in both U87 and T98G cells and reduced the basal level of p53 in U87 cells, indicating that p53 played no role in the vorinostat-induced apoptosis. To clearly define the role of p53 in bortezomib- and doxorubicin-induced apoptosis, we combined doxorubicin with bortezomib to treat U87 cells to assess this combination's effect on apoptosis and p53 status. Interestingly, the combination of doxorubicin with bortezomib engendered compound stress, resulting in a synergistic outcome for apoptosis in U87 cells. However, the amounts of p53 in the total count and in the nucleus were much lower with the combination than with doxorubicin alone, suggesting that p53 played no role in either the compound stress, doxorubicin-only or bortezomib-induced apoptosis.
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http://dx.doi.org/10.1080/15384101.2022.2041954 | DOI Listing |
Bioorg Chem
December 2024
Department of Pharmaceutics, College of Pharmacy, King Khalid University, Abha 62529, Saudi Arabia.
Red grapes contain resveratrol (Resv), a polyphenol with anti-inflammatory, anti-diabetic, and anticancer properties. In this study, in silico molecular docking was used to assess the binding affinity of Resv to target proteins. Resv was encapsulated in PEGylated liposomes (LNPs) using Phospholipon 90G, cholesterol, and DSPE-mPEG.
View Article and Find Full Text PDFAdv Healthc Mater
December 2024
Department of Medical Physics, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, 730000, China.
PEGylated liposomes can deliver anti-cancer drugs to brain tumors, and achieve enhanced permeability and retention effects. Triggering receptor expressed on myeloid cells 2 (TREM2) is an excellent biomarker for precise therapy of glioma. The present study is aimed at designing PEGylated nanoliposomal doxorubicin (PLD) conjugated with peptides targeting TREM2 for glioma-targeting therapy.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
December 2024
The Rappaport Faculty of Medicine and Research Institute, and the Rappaport Technion Integrated Cancer Center (R-TICC), Technion-Israel Institute of Technology, Haifa 3109601, Israel.
Cytokines constitute a family of proteins that modulate the immune system and are secreted by many cells. CXCL12, along with its receptor CXCR4, are essential players in numerous processes. Dysregulation of their function underlie the mechanism(s) of several pathologies, including malignancies.
View Article and Find Full Text PDFCancers (Basel)
November 2024
Department of Chemical, Biological, Pharmaceutical, Environmental Science, University of Messina, Viale Ferdinando Stagno d'Alcontres, 31, 98166 Messina, Italy.
In oncology, casein kinase 2 (CK2), a serine/threonine kinase, has a dual action, regulating cellular processes and acting as an oncogenic promoter. : This study examined the effect of CX-4945, a selective CK2 inhibitor, in a human U-87 glioblastoma (GBM) cell line, treated with CX-4945 (5, 10, and 15 μM) for 24 h. Similarly, the hCMEC/D3 cell line was used to mimic the blood-brain barrier (BBB), examining the ability of CX-4945 to restore BBB homeostasis, after stimulation with lipopolysaccharide (LPS) and then treated with CX-4945 (5, 10, and 15 μM).
View Article and Find Full Text PDFGene
February 2025
Department of Otorhinolaryngology Head and Neck Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. Electronic address:
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