ArticleOncotarget2014
Novel combination of mitochondrial division inhibitor 1 (mdivi-1) and platinum agents produces synergistic pro-apoptotic effect in drug resistant tumor cells.
Article in Oncotarget, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
61 citing papers in PubMed, 100 citations in OpenAlex.
- Mitochondrial dynamics: A promising tool for personalized TNBC management.Genes & diseases · 2026Review
- Mitochondrial dynamics and cancer: mechanisms and targeted therapy.Cell biology and toxicology · 2026Review
- Targeting mitochondria as a potential therapeutic strategy against radioresistance in cancer.Frontiers in oncology · 2026Review
- Subcellular Stress Markers in Epithelial Ovarian Cancer.International journal of molecular sciences · 2025Review
- Quinazolinone derivatives as potential anti‑tumor agents: Structural features and molecular mechanisms in inducing cell death (Review).International journal of molecular medicine · 2025Review
- Article
- Mitochondrial dynamics in cisplatin resistance: molecular mechanisms and therapeutic targeting.Frontiers in oncology · 2025Review
- Molecular Modulators and Receptors of Selective Autophagy: Disease Implication and Identification Strategies.International journal of biological sciences · 2024Review
- Inhibition of Drp1 orchestrates the responsiveness of breast cancer cells to paclitaxel but insignificantly relieves paclitaxel-related ovarian damage in mice.Scientific reports · 2023Article
- Transcription Factors Tec1 and Tec2 Play Key Roles in the Hyphal Growth and Virulence of Mucor lusitanicus Through Increased Mitochondrial Oxidative Metabolism.Journal of microbiology (Seoul, Korea) · 2023Article
- Z-Ligustilide Combined with Cisplatin Reduces PLPP1-Mediated Phospholipid Synthesis to Impair Cisplatin Resistance in Lung Cancer.International journal of molecular sciences · 2023Article
- Blood Serum Stimulates the Virulence Potential of Mucorales through Enhancement in Mitochondrial Oxidative Metabolism and Rhizoferrin Production.Journal of fungi (Basel, Switzerland) · 2023Article
- Mitochondrial dynamics in health and disease: mechanisms and potential targets.Signal transduction and targeted therapy · 2023Review
- Photochemical Targeting of Mitochondria to Overcome Chemoresistance in Ovarian CancerPhotochemistry and photobiology · 2023Review
- Mitophagy: A novel perspective for insighting into cancer and cancer treatment.Cell proliferation · 2022Review
- Mitochondrial Dynamin-Related Protein Drp1: a New Player in Cardio-oncology.Current oncology reports · 2022Review
- The Non-Specific Drp1 Inhibitor Mdivi-1 Has Modest Biochemical Antioxidant Activity.Antioxidants (Basel, Switzerland) · 2022Article
- Extracellular Vesicles and Resistance to Anticancer Drugs: A Tumor Skeleton Key for Unhinging Chemotherapies.Frontiers in oncology · 2022Review
- Review
- Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
Overcoming platinum drug resistance represents a major clinical challenge in cancer treatment. We discovered a novel drug combination using cisplatin and a class of thioquinazolinone derivatives including mdivi-1 (mitochondrial division inhibitor-1), that induces synergistic apoptosis in platinum resistant tumor cells, including those from cisplatin-refractory endstage ovarian cancer patients. However, through study of the combination effect on Drp1 (the reported target of mdivi-1) knockout MEF cells and the functional analysis of mdivi-1 analogs, we revealed that the synergism between mdivi-1 and cisplatin is Drp1-independent. Mdivi-1 impairs DNA replication and its combination with cisplatin induces a synergistic increase of replication stress and DNA damage, causing a preferential upregulation of a BH3-only protein Noxa. Mdivi-1 also represses mitochondrial respiration independent of Drp1, and the combination of mdivi-1 and cisplatin triggers substantial mitochondrial uncoupling and swelling. Upregulation of Noxa and simultaneous mitochondrial swelling causes synergistic induction of mitochondrial outer membrane permeabilization (MOMP), proceeding robust mitochondrial apoptotic signaling independent of Bax/Bak. Thus, the novel mode of MOMP induction by the combination through the "dual-targeting" potential of mdivi-1 on DNA replication and mitochondrial respiration suggests a novel class of compounds for platinum-based combination option in the treatment of platinum as well as multidrug resistant tumors.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.