ArticleCell communication and signaling : CCS2018
DNA damage and apoptosis induced by a potent orally podophyllotoxin derivative in breast cancer.
Article in Cell communication and signaling : CCS, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 27 citations in OpenAlex.
- Exploiting Metabolic Vulnerabilities in Acute Myeloid Leukemia: Rationale and Evidence for Combining Metabolic Modulators with Conventional Chemotherapy.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Abietic Acid Induces DNA Damage and Cell Apoptosis in Lung Cancer Cells Through Targeting TOP2A.Biomolecules · 2025Article
- Podophyllic Aldehyde, a Podophyllotoxin Derivate, Elicits Different Cell Cycle Profiles Depending on the Tumor Cell Line: A Systematic Proteomic Analysis.International journal of molecular sciences · 2024Article
- Podophyllotoxin: Recent Advances in the Development of Hybridization Strategies to Enhance Its Antitumoral Profile.Pharmaceutics · 2023Review
- Chronic restraint stress promotes gastric epithelial malignant transformation by activating the Akt/p53 signaling pathway via ADRB2.Oncology letters · 2022Article
- Discovery of Quinacrine as a Potent Topo II and Hsp90 Dual-Target Inhibitor, Repurposing for Cancer Therapy.Molecules (Basel, Switzerland) · 2022Article
- Identification of Novel 4'-Molecules (Basel, Switzerland) · 2022Article
- Ciclopirox Olamine Exerts Tumor-Suppressor EffectsFrontiers in oncology · 2022Article
- Podofilox suppresses gastric cancer cell proliferation by regulating cell cycle arrest and the c-Myc/ATG10 axis.Experimental and therapeutic medicine · 2021Article
- Proliferation, migration and invasion of triple negative breast cancer cells are suppressed by berbamine via the PI3K/Akt/MDM2/p53 and PI3K/Akt/mTOR signaling pathways.Oncology letters · 2021Article
- Insight Into the Molecular Mechanism of Podophyllotoxin Derivatives as Anticancer Drugs.Frontiers in cell and developmental biology · 2021Review
- WRN inhibits oxidative stress-induced apoptosis of human lensepithelial cells through ATM/p53 signaling pathway and its expression is downregulated by DNA methylation.Molecular medicine (Cambridge, Mass.) · 2020Article
- Podophyllotoxin Exposure Causes Spindle Defects and DNA Damage-Induced Apoptosis in Mouse Fertilized Oocytes and Early Embryos.Frontiers in cell and developmental biology · 2020Article
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundTargeting TopoisomeraseII (TopoII) and generate enzyme mediated DNA damage is an effective strategy for treatment of breast cancer. TopoII is known as a validated target for drug discovery and cancer chemotherapy.
methodsXWL-1-48, a new orally podophyllotoxin derivative, was designed and synthesized. The effect of XWL-1-48 on TopoII binding and activity was determined by molecular docking software and kDNA-decatenation assay, respectively. In vitro and in vivo breast cancer models were used to document the antitumor activity of XWL-1-48. Cellular apoptosis, cell cycle and ROS were analyzed by flow cytometry. Alteration of XWL-1-48-mediated downstream pathways was determined by western blot analysis.
resultsThe cytotoxicity of XWL-1-48 is more potent than that of its congener GL331. Molecular docking demonstrated that XWL-1-48 could bind to TopoII through forming two strong hydrogen bonds and potential pi-pi interactions. Noticeably, XWL-1-48 exerts potent antitumor activity in in vitro and in vivo breast cancer model. Treatment with XWL-1-48 caused ROS generation and triggered DNA damage through induction of γ-H2AX and activation of ATM/p53/p21 pathway. Further studies showed that XWL-1-48 led to S-phase arrest and mitochondrial apoptosis. Meanwhile, XWL-1-48 significantly blocked PI3K/Akt/Mdm2 pathway and enhanced Mdm2 degradation.
conclusionXWL-1-48 may be a promising orally topoII inhibitor, its mechanisms are associated with suppression of TopoII, induction of DNA damage and apoptosis, blockage of PI3K/AKT/Mdm2 pathway.
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