ArticleBiochemical pharmacology2018
Opening of voltage dependent anion channels promotes reactive oxygen species generation, mitochondrial dysfunction and cell death in cancer cells.
Article in Biochemical pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 120 papers, 1 of them a synthesis that pooled it.
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Who cites it
120 citing papers in PubMed, 1 synthesis or guideline pooled it, 207 citations in OpenAlex.
- Ferroptosis and ferritinophagy in diabetes complications.Molecular metabolism · 2022Pooled it
- Ferroptosis in liver biology and diseases.Hepatology communications · 2026Review
- Acupuncture suppresses the endoplasmic reticulum stress-c-Jun N-terminal kinase pathway to inhibit chondrocyte apoptosis and attenuate knee osteoarthritis.Cell stress & chaperones · 2026Article
- Target FADS1-arachidonic acid-ferroptosis axis: A metabolic bridge linking matrix stiffness to PDAC stemness.Materials today. Bio · 2026Article
- Molecular mechanisms of iron metabolism and ferroptosis in cardiovascular diseases and intervention strategies targeting natural products (Review).Molecular medicine reports · 2026Review
- PFAS Exposure and Metabolic Disorders: Mechanistic Insights into Lipid and Glucose Homeostasis.Biomolecules · 2026Review
- Article
- The Gluco-Vascular Injury Axis in Diabetic Cardiovascular Dysfunction: A Narrative Review.Cureus · 2026Review
- Anti-cancer drugs targeting the NADH-binding site of VDAC rewire channel electrophysiology and partially suppress cation selectivity.The FEBS journal · 2026Article
- VDAC2: an emerging pivotal and multifaceted regulator in tumor biology.Apoptosis : an international journal on programmed cell death · 2026Review
- Inhibition of MID1IP1 induces ferroptosis and suppresses c-Myc expression in colorectal cancer cell.Genes & genomics · 2026Article
- Low-dose Simvastatin protects pancreatic cancer cells by promoting mitochondrial autophagy through TFEB.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Ferroptosis in cancer toward molecular insights and clinical translation in pancreatic cancer.Molecular cancer · 2026Review
- Ginsenoside Rg1 antagonizes diabetic osteoporosis by regulating ferroptosis via mitochondrial membrane potential in H-type vascular endothelial cells.Frontiers in aging · 2026Article
- Alpha-linolenic acid protects against heatstroke-induced acute lung injury by inhibiting ferroptosis through Nrf2 activation.Redox report : communications in free radical research · 2025Article
- Mitochondria-Mediated Mechanisms of Ferroptosis in Neurological Diseases.Neurochemical research · 2025Review
- From mitochondrial dysregulation to ferroptosis: Exploring new strategies and challenges in radioimmunotherapy (Review).International journal of oncology · 2025Review
- Targeting ATF4-DDIT4/TXNIP induced mitochondrial dysfunction and ferroptosis: ISRIB as novel therapy for septic cardiomyopathy.Journal of translational medicine · 2025Article
- Review
- Cancer stem cells: mitochondria signalling pathway and strategies for therapeutic interventions.Molecular biology reports · 2025Review
60 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 1 institution in 2 countries.
Funding
Abstract
Enhancement of aerobic glycolysis and suppression of mitochondrial metabolism characterize the pro-proliferative Warburg phenotype of cancer cells. High free tubulin in cancer cells closes voltage dependent anion channels (VDAC) to decrease mitochondrial membrane potential (ΔΨ), an effect antagonized by erastin, the canonical promotor of ferroptosis. Previously, we identified six compounds (X1-X6) that also block tubulin-dependent mitochondrial depolarization. Here, we hypothesized that VDAC opening after erastin and X1-X6 increases mitochondrial metabolism and reactive oxygen species (ROS) formation, leading to ROS-dependent mitochondrial dysfunction, bioenergetic failure and cell death. Accordingly, we characterized erastin and the two most potent structurally unrelated lead compounds, X1 and X4, on ROS formation, mitochondrial function and cell viability. Erastin, X1 and X4 increased ΔΨ followed closely by an increase in mitochondrial ROS generation within 30-60 min. Subsequently, mitochondria began to depolarize after an hour or longer indicative of mitochondrial dysfunction. N-acetylcysteine (NAC, glutathione precursor and ROS scavenger) and MitoQ (mitochondrially targeted antioxidant) blocked increased ROS formation after X1 and prevented mitochondrial dysfunction. Erastin, X1 and X4 selectively promoted cell killing in HepG2 and Huh7 human hepatocarcinoma cells compared to primary rat hepatocytes. X1 and X4-dependent cell death was blocked by NAC. These results suggest that ferroptosis induced by erastin and our erastin-like lead compounds was caused by VDAC opening, leading to increased ΔΨ, mitochondrial ROS generation and oxidative stress-induced cell death.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.