AI Article Synopsis
Article Abstract
Glioma is recognized as one of the most lethal and aggressive brain tumors. Although the standard-of-care treatment for glioblastoma (GBM) involves maximal surgical resection and temozolomide (TMZ) chemotherapy, the discovery of novel anti-tumor agents from nature sources is an effective strategy for glioma treatment. In this study, we conducted a screening process to identify the bisindole alkaloid melodinine J (MDJ) from Melodinus tenuicaudatus. We assessed its potency in overcoming TMZ resistance in patient-derived recurrent glioma strains, TMZ-resistant cell lines, and nude mouse tumor models of glioma cells. Our results first indicated that MDJ effectively inhibited malignancy and stimulated apoptosis in glioma. Mechanistic studies revealed that MDJ triggered deadly mitochondrial dysfunction and apoptosis by disrupting cross-organellar communication between the endoplasmic reticulum (ER) and mitochondria-associated membranes (MAMs). We also showed that high levels of TMX1 may promote malignancy of glioma by ER-mitochondria communications, bioenergetics efficiency, and tumor growth. Overall, our study proved that MDJ interfered the function of TMX1-mediated MAM networks, thereby overcoming the proliferation and chemo-resistance of glioma cells.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/ptr.8396 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Activated kynurenine pathway metabolism by YKL-40 establishes an inhibitory immune microenvironment and drives glioblastoma development.
Cell 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.
Vincristine exerts antiglioma effects by inhibiting the PI3K/AKT signaling pathway: A mechanistic study based on network pharmacology, bioinformatics analysis, and experimental validation.
Naunyn Schmiedebergs Arch Pharmacol
December 2024
Department of Neurosurgery, the Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Donghu District, Nanchang City, Jiangxi, 330006, China.
In clinical settings, glioma patients often develop secondary resistance to first-line chemotherapy drugs. Vincristine has been reported for its application in cancer chemotherapy, but its molecular mechanism of action remains unclear. This study aimed to identify potential targets of vincristine in glioma using network pharmacology and to experimentally validate the possible molecular mechanisms against glioma.
View Article and Find Full Text PDFA Role for the Hippo/YAP1 Pathway in the Regulation of In Vitro Vasculogenic Mimicry in Glioblastoma Cells.
J Cell Mol Med
December 2024
Laboratoire d'Oncologie Moléculaire, Département de Chimie, Université du Québec à Montréal, Montreal, Quebec, Canada.
The Hippo pathway plays a tumorigenic role in highly angiogenic glioblastoma (GBM), whereas little is known about clinically relevant Hippo pathway inhibitors' ability to target adaptive mechanisms involved in GBM chemoresistance. Their molecular impact was investigated here in vitro against an alternative process to tumour angiogenesis termed vasculogenic mimicry (VM) in GBM-derived cell models. In silico analysis of the downstream Hippo signalling members YAP1, TAZ and TEAD1 transcript levels in low-grade glioblastoma (LGG) and GBM tumour tissues was performed using GEPIA.
View Article and Find Full Text PDFComprehensive evaluation of EGFR and AKT targeting efficacy of resveratrol loaded PEGylated liposomes for the glioblastoma management: In silico, in vitro BBB permeation studies.
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 PDFNanoparticle-enhanced delivery of resveratrol for targeted therapy of glioblastoma: Modulating the Akt/GSK-3β/NF-kB pathway in C6 glioma cells.
Brain Res
December 2024
Molecular and Cellular Biology Laboratory, Department of Pharmacology, NIIMS Institute of Pharmacy, NIIMS University Jaipur, Rajasthan, India. Electronic address:
Objective: The study aims to explore Resveratrol (RES) as a potential therapeutic agent for Glioblastoma multiforme (GBM), a challenging brain cancer. RES, a polyphenolic compound with known benefits in various diseases including cancer, has shown promise in inhibiting glioma progression through its effects on the AKT signaling pathways. However, its limited ability to cross the blood-brain barrier restricts its clinical application in GBM treatment.
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!