ArticleCell communication and signaling : CCS2019
TPP-related mitochondrial targeting copper (II) complex induces p53-dependent apoptosis in hepatoma cells through ROS-mediated activation of Drp1.
Article in Cell communication and signaling : CCS, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 54 citations in OpenAlex.
- From 2D to 3D Colorectal Cancer Patient-Derived Organoids (PDOs) and In Vivo Models: Copper(II) Complexes as Promising New Antitumor Agents.Journal of medicinal chemistry · 2026Article
- On the Edge of Benefit and Harm: Reactive Oxygen Species in Cancer.International journal of molecular sciences · 2026Review
- Article
- Interplay of oxidative stress and antioxidant mechanisms in cancer development and progression.Archives of toxicology · 2026Review
- Targeting cuproptosis in liver cancer: Molecular mechanisms and therapeutic implications.Apoptosis : an international journal on programmed cell death · 2025Review
- Anticancer Activity ofBiomolecules · 2025Article
- The spatiotemporal heterogeneity of reactive oxygen species in the malignant transformation of viral hepatitis to hepatocellular carcinoma: a new insight.Cellular & molecular biology letters · 2025Review
- Innovative Approaches in the Synthesis and Optimization of Copper Complexes for Antitumor Therapies: A Comprehensive Review.Molecules (Basel, Switzerland) · 2025Review
- Copper(II) Complexes with 2,2':6',2″-Terpyridine Derivatives Displaying Dimeric Dichloro-μ-Bridged Crystal Structure: Biological Activities from 2D and 3D Tumor Spheroids to In Vivo Models.Journal of medicinal chemistry · 2024Article
- Recently Reported Biological Activities and Action Targets of Pt(II)- and Cu(II)-Based Complexes.Molecules (Basel, Switzerland) · 2024Review
- Identification of Copper Homeostasis-Related Gene Signature for Predicting Prognosis in Patients with Epithelial Ovarian Cancer.Cancer informatics · 2024Article
- Copper(II) Complexes with 1-(Isoquinolin-3-yl)heteroalkyl-2-ones: Synthesis, Structure and Evaluation of Anticancer, Antimicrobial and Antioxidant Potential.International journal of molecular sciences · 2023Article
- Iron and copper: critical executioners of ferroptosis, cuproptosis and other forms of cell death.Cell communication and signaling : CCS · 2023Review
- Review
- Synthesis, Structure and Cytotoxic Properties of Copper(II) Complexes of 2-Iminocoumarins Bearing a 1,3,5-Triazine or Benzoxazole/Benzothiazole Moiety.Molecules (Basel, Switzerland) · 2022Article
- In Vitro Effects of Mitochondria-Targeted Antioxidants in a Small-Cell Carcinoma of the Ovary of Hypercalcemic Type and in Type 1 and Type 2 Endometrial Cancer.Biomedicines · 2022Article
- Very early environmental enrichment protects against apoptosis and improves functional recovery from hypoxic-ischemic brain injury.Frontiers in molecular neuroscience · 2022Article
- Metal Complexes or Chelators with ROS Regulation Capacity: Promising Candidates for Cancer Treatment.Molecules (Basel, Switzerland) · 2021Review
- Molecular Dynamics Simulation of 2-Benzimidazolyl-Urea with DPPC Lipid Membrane and Comparison with a Copper(II) Complex Derivative.Membranes · 2021Article
- High expression of PARD3 predicts poor prognosis in hepatocellular carcinoma.Scientific reports · 2021Article
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIn recent years, copper complexes have gradually become the focus of potential anticancer drugs due to their available redox properties and low toxicity. In this study, a novel mitochondrion-targeting copper (II) complex, [Cu (ttpy-tpp)Br
methodsMultiple molecular experiments including Flow cytometry, Western blot, Immunofluorescence, Tracker staining, Transmission Electron Microscopy and Molecular docking simulation were used to elucidate the underlying mechanisms. Human hepatoma cells were subcutaneously injected into right armpit of male nude mice for evaluating the effects of CTB in vivo.
resultsCTB induced apoptosis via collapse of mitochondrial membrane potential (MMP), ROS production, Bax mitochondrial aggregation as well as cytochrome c release, indicating that CTB-induced apoptosis was associated with mitochondrial pathway in human hepatoma cells. Mechanistic study revealed that ROS-related mitochondrial translocation of p53 was involved in CTB-mediated apoptosis. Simultaneously, elevated mitochondrial Drp1 levels were also observed, and interruption of Drp1 activation played critical role in p53-dependent apoptosis. CTB also strongly suppressed the growth of liver cancer xenografts in vivo.
conclusionIn human hepatoma cells, CTB primarily induces mitochondrial dysfunction and promotes accumulation of ROS, leading to activation of Drp1. These stimulation signals accelerate mitochondrial accumulation of p53 and lead to the eventual apoptosis. Our research shows that CTB merits further evaluation as a chemotherapeutic agent for the treatment of Hepatocellular carcinoma (HCC).
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