ArticleCell death & disease2018
A novel ruthenium complex with xanthoxylin induces S-phase arrest and causes ERK1/2-mediated apoptosis in HepG2 cells through a p53-independent pathway.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 51 citations in OpenAlex.
- Antitumor Effect of Ruthenium(II) with 2‑Mercaptothiazoline Ligand Complex in Murine Melanoma Model.ACS omega · 2026Article
- Correlational Analysis of Liver Metabolites and Pharmacodynamic Indexes in Xanthoxylin-Treated Acute Liver Failure.Molecules (Basel, Switzerland) · 2026Article
- The LncRNA GABARAPL3/miR-155-5p axis modulates the proliferation and invasion of liver cancer cells by regulating GABARAPL1.Molecular biology reports · 2025Article
- Cyclodextrin-Based Metal-Organic Framework as an Application Platform for Bioactive Ruthenium(III) Complexes.Inorganic chemistry · 2025Article
- Xanthoxyline prevents aging and neuronal damage by activating autophagy and DAF-16 expression inAnimal cells and systems · 2025Article
- Ru(II)-based complexes containing 2-thiouracil derivatives suppress liver cancer stem cells by targeting NF-κB and Akt/mTOR signaling.Cell death discovery · 2024Article
- A Review of the Ethnobotanical Use, Chemistry and Pharmacological Activities of Constituents Derived from the Plant GenusMetabolites · 2024Review
- A novel ruthenium complex with 5-fluorouracil suppresses colorectal cancer stem cells by inhibiting Akt/mTOR signaling.Cell death discovery · 2023Article
- New ruthenium-xanthoxylin complex eliminates colorectal cancer stem cells by targeting the heat shock protein 90 chaperone.Cell death & disease · 2023Article
- An Overview of the Potential Medicinal and Pharmaceutical Properties of Ru(II)/(III) Complexes.International journal of molecular sciences · 2023Review
- Molecular Design, Spectroscopic, DFT, Pharmacological, and Molecular Docking Studies of Novel Ruthenium(III)-Schiff Base Complex: An Inhibitor of Progression in HepG2 Cells.International journal of environmental research and public health · 2022Article
- Biological Investigations of Ru(II) Complexes With Diverse β-diketone Ligands.European journal of inorganic chemistry · 2021Article
- Organoruthenium Complexes with Benzo-Fused Pyrithiones Overcome Platinum Resistance in Ovarian Cancer Cells.Cancers · 2021Article
- Guided Antitumoural Drugs: (Imidazol-2-ylidene)(L)gold(I) Complexes Seeking Cellular Targets Controlled by the Nature of Ligand L.Chemistry (Weinheim an der Bergstrasse, Germany) · 2021Article
- Avobenzone incorporation in a diverse range of Ru(II) scaffolds produces potent potential antineoplastic agents.Dalton transactions (Cambridge, England : 2003) · 2020Article
- Article
- Pterostilbene Enhances Cytotoxicity and Chemosensitivity in Human Pancreatic Cancer Cells.Biomolecules · 2020Article
- Ru(II) Complexes Bearing O, O-Chelated Ligands Induced Apoptosis in A549 Cells through the Mitochondrial Apoptotic Pathway.Bioinorganic chemistry and applications · 2020Article
- Article
- Ru(II)-thymine complex causes DNA damage and apoptotic cell death in human colon carcinoma HCT116 cells mediated by JNK/p38/ERK1/2 via a p53-independent signaling.Scientific reports · 2019Article
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ruthenium-based compounds have gained great interest due to their potent cytotoxicity in cancer cells; however, much of their potential applications remain unexplored. In this paper, we report the synthesis of a novel ruthenium complex with xanthoxylin (RCX) and the investigation of its cellular and molecular action in human hepatocellular carcinoma HepG2 cells. We found that RCX exhibited a potent cytotoxic effect in a panel of cancer cell lines in monolayer cultures and in a 3D model of multicellular cancer spheroids formed from HepG2 cells. This compound is detected at a high concentration in the cell nuclei, induces DNA intercalation and inhibits DNA synthesis, arresting the cell cycle in the S-phase, which is followed by the activation of the caspase-mediated apoptosis pathway in HepG2 cells. Gene expression analysis revealed changes in the expression of genes related to cell cycle control, apoptosis and the MAPK pathway. In addition, RCX induced the phosphorylation of ERK1/2, and pretreatment with U-0126, an MEK inhibitor known to inhibit the activation of ERK1/2, prevented RCX-induced apoptosis. In contrast, pretreatment with a p53 inhibitor (cyclic pifithrin-α) did not prevent RCX-induced apoptosis, indicating the activation of a p53-independent apoptosis pathway. RCX also presented a potent in vivo antitumor effect in C.B-17 SCID mice engrafted with HepG2 cells. Altogether, these results indicate that RCX is a novel anticancer drug candidate.
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