ArticleInternational journal of molecular sciences2016
Mobilization of Intracellular Copper by Gossypol and Apogossypolone Leads to Reactive Oxygen Species-Mediated Cell Death: Putative Anticancer Mechanism.
Article in International journal of molecular sciences, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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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.
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Who cites it
12 citing papers in PubMed, 22 citations in OpenAlex.
- Copper death combination therapy: the innovative frontier and challenges in prostate cancer treatment.Cancer biology & therapy · 2025Review
- Revisiting the antioxidant-prooxidant conundrum in cancer research.Medical oncology (Northwood, London, England) · 2024Article
- Current state of research on copper complexes in the treatment of breast cancer.Open life sciences · 2024Review
- Soy Isoflavones Induce Cell Death by Copper-Mediated Mechanism: Understanding Its Anticancer Properties.Molecules (Basel, Switzerland) · 2023Article
- Gossypol and Its Natural Derivatives: Multitargeted Phytochemicals as Potential Drug Candidates for Oncologic Diseases.Pharmaceutics · 2022Review
- Understanding the Prooxidant Action of Plant Polyphenols in the Cellular Microenvironment of Malignant Cells: Role of Copper and Therapeutic Implications.Frontiers in pharmacology · 2022Review
- Pomegranate juice anthocyanidins induce cell death in human cancer cells by mobilizing intracellular copper ions and producing reactive oxygen species.Frontiers in oncology · 2022Article
- Targeting Protein Neddylation to Inactivate Cullin-RING Ligases by Gossypol: A Lucky Hit or a New Start?Drug design, development and therapy · 2021Review
- Baicalein, as a Prooxidant, Triggers Mitochondrial Apoptosis in MCF-7 Human Breast Cancer Cells Through Mobilization of Intracellular Copper and Reactive Oxygen Species Generation.OncoTargets and therapy · 2019Article
- Isolation of Cottonseed Extracts That Affect Human Cancer Cell Growth.Scientific reports · 2018Article
- Cancer Chemoprevention by Phytochemicals: Nature's Healing Touch.Molecules (Basel, Switzerland) · 2017Review
- Hydroxytyrosol Induces Apoptosis and Cell Cycle Arrest and Suppresses Multiple Oncogenic Signaling Pathways in Prostate Cancer Cells.Nutrition and cancerArticle
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 5 countries.
Funding
Abstract
There is compelling evidence that serum, tissue and intracellular levels of copper are elevated in all types of cancer. Copper has been suggested as an important co-factor for angiogenesis. It is also a major metal ion present inside the nucleus, bound to DNA bases, particularly guanine. We have earlier proposed that the interaction of phenolic-antioxidants with intracellular copper leads to the generation of reactive oxygen species (ROS) that ultimately serve as DNA cleaving agents. To further validate our hypothesis we show here that the antioxidant gossypol and its semi-synthetic derivative apogossypolone induce copper-mediated apoptosis in breast MDA-MB-231, prostate PC3 and pancreatic BxPC-3 cancer cells, through the generation of ROS. MCF10A breast epithelial cells refractory to the cytotoxic property of these compounds become sensitized to treatment against gossypol, as well as apogossypolone, when pre-incubated with copper. Our present results confirm our earlier findings and strengthen our hypothesis that plant-derived antioxidants mobilize intracellular copper instigating ROS-mediated cellular DNA breakage. As cancer cells exist under significant oxidative stress, this increase in ROS-stress to cytotoxic levels could be a successful anticancer approach.
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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.