Drastic surges in intracellular reactive oxygen species (ROS) induce cell apoptosis, while most chemotherapy drugs lead to the accumulation of ROS. Here, we constructed an organic compound, arsenical -(4-(1,3,2-dithiarsinan-2-yl)phenyl)acrylamide (AAZ2), which could prompt the ROS to trigger mitochondrial-dependent apoptosis in gastric cancer (GC). Mechanistically, by targeting pyruvate dehydrogenase kinase 1 (PDK1), AAZ2 caused metabolism alteration and the imbalance of redox homeostasis, followed by the inhibition of phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway and leading to the activation of B-cell lymphoma 2 (Bcl2)/Bcl2-associated X (Bax)/caspase-9 (Cas9)/Cas3 cascades. Importantly, our in vivo data demonstrated that AAZ2 could inhibit the growth of GC xenograft. Overall, our data suggested that AAZ2 could contribute to metabolic abnormalities, leading to mitochondrial-dependent apoptosis by targeting PDK1 in GC.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10014317 | PMC |
| http://dx.doi.org/10.1631/jzus.B2200351 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Dried Apricot Polyphenols Suppress the Growth of A549 Human Lung Adenocarcinoma Cells by Inducing Apoptosis via a Mitochondrial-Dependent Pathway.
Foods
January 2025
Xinjiang Key Laboratory of Biological Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi 830017, China.
Dried apricots are rich in a variety of polyphenols, which have anti-cancer activity. In this study, 949 phenolic substances were found by means of UPLC-MS/MS, mainly including 2',7-dihydroxy-3',4'-dimethoxyisoflavan, scopoletin, rutin, quercetin-3-O-robinobioside, and elaidolinolenic acid. The results indicated that dried apricot polyphenols (DAPs) could cause cell cycle arrest in the G0/G1 and G2/M phases by decreasing the cyclin D1, CDK4, cyclin B1, CDK1, and CDK6 levels in A549 human lung adenocarcinoma cells.
View Article and Find Full Text PDFDnmt3a-mediated DNA Methylation Regulates P. gingivalis-suppressed Cementoblast Mineralization Partially Via Mitochondria-dependent Apoptosis Pathway.
Inflammation
January 2025
State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China.
Background: DNA methyltransferase 3A (Dnmt3a) is an enzyme that catalyzes the de novo methylation of DNA, and plays essential roles in a wide range of physiological and pathological processes. However, it remains unclear whether Porphyromonas gingivalis affects cementoblasts, the cells responsible for cementum formation, through Dnmt3a.
Methods: The samples were collected from models of mouse periapical lesions and mice of different ages, and the expression of Dnmt3a was detected through immunofluorescence.
Polymeric Nanoparticles Potentiate the Anticancer Activity of Novel PI3Kα Inhibitors Against Triple-Negative Breast Cancer Cells.
Biomedicines
November 2024
Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman 11733, Jordan.
: Dysregulation in phosphoinositide-3-kinase alpha (PI3Kα) signaling is implicated in the development of various cancers, including triple-negative breast cancer (TNBC). We have previously synthesized a series of N-phenyl-6-chloro-4-hydroxy-2-quinolone-3-carboxamides as targeted inhibitors against PI3Kα. Herein, two drug candidates, R7 and R11, were selected to be further investigated as a nanoparticle (NP) formulation against TNBC.
View Article and Find Full Text PDFTargeting PGAM5 attenuates airway inflammation in asthma by inhibiting HMGB1 release in bronchial epithelium.
Free Radic Biol Med
January 2025
Chronic Airways Diseases Laboratory, Department of Respiratory and Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. Electronic address:
Article Synopsis
- Previous studies linked high HMGB1 levels to the development of steroid-insensitive asthma caused by toluene diisocyanate (TDI), highlighting mitochondrial dysfunction in bronchial epithelia.
- This study aims to determine if PGAM5, a mitochondrial protein, influences HMGB1 release in TDI-induced asthma by comparing its levels in asthma patients and healthy individuals and conducting various animal and in vitro experiments.
- Findings showed that inhibiting PGAM5 reduced airway inflammation and HMGB1 release in TDI-exposed mice, illustrating a potential regulatory mechanism involving mitochondrial apoptosis-related processes.
Doublecortin regulates the mitochondrial-dependent apoptosis in glioma via Rho-A/Net-1/p38-MAPK signaling.
Mol Med
December 2024
Department of Neurobiology and Anatomy, Key Laboratory of Neurobiology, Xuzhou Medical University, 209, Tongshan Road, Xuzhou, 221004, China.
Doublecortin (DCX) is a microtubule-associated protein known to be a key regulator of neuronal migration and differentiation during brain development. However, the role of DCX, particularly in regulating the survival and growth of glioma cells, remains unclear. In this study, we utilized CRISPR/Cas9 technology to knock down DCX in the human glioma cell line (U251).
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!