ArticlePloS one2014
Cucurbitacin B induced ATM-mediated DNA damage causes G2/M cell cycle arrest in a ROS-dependent manner.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed.
- Cucurbitacin B Promotes Tumor Necrosis Factor Receptor 1 Ectodomain Shedding by Selectively Activating the Extracellular Signal-Regulated Kinase Signaling Pathway.International journal of molecular sciences · 2026Article
- Article
- Recent Advances in the Application of Cucurbitacin B as an Anticancer Agent.International journal of molecular sciences · 2025Review
- Autophagy inhibition induced by EM-2 augments apoptosis via ROS-mediated ATM-Chk2-p53-p21 and MAPK pathway in lung and breast carcinoma.Frontiers in pharmacology · 2025Article
- Antiinflammatory effects of cucurbitacins and sorafenib in Hepg2 cells by modulating the IκB/NF-κB/COX-2 pathway through Akt signaling.Turkish journal of biology = Turk biyoloji dergisi · 2025Article
- Article
- PSPC1 Inhibition Synergizes with Poly(ADP-ribose) Polymerase Inhibitors in a Preclinical Model of BRCA-Mutated Breast/Ovarian Cancer.International journal of molecular sciences · 2023Article
- Review
- Antitumor activity and mechanism of cucurbitacin B in A549/DDP cells.Naunyn-Schmiedeberg's archives of pharmacology · 2023Article
- Iberverin exhibits antineoplastic activities against human hepatocellular carcinoma via DNA damage-mediated cell cycle arrest and mitochondrial-related apoptosis.Frontiers in pharmacology · 2023Article
- Cucurbitacins as Potent Chemo-Preventive Agents: Mechanistic Insight and Recent Trends.Biomolecules · 2022Review
- Cytochrome B5 type A alleviates HCC metastasis via regulating STOML2 related autophagy and promoting sensitivity to ruxolitinib.Cell death & disease · 2022Article
- pH and ROS sequentially responsive podophyllotoxin prodrug micelles with surface charge-switchable and self-amplification drug release for combating multidrug resistance cancer.Drug delivery · 2021Article
- Use of cucurbitacins for lung cancer research and therapy.Cancer chemotherapy and pharmacology · 2021Review
- Perspectives on natural compounds in chemoprevention and treatment of cancer: an update with new promising compounds.European journal of cancer (Oxford, England : 1990) · 2021Review
- The Effect of Terpenoid Natural Chinese Medicine Molecular Compound on Lung Cancer Treatment.Evidence-based complementary and alternative medicine : eCAM · 2021Review
- PP2A and tumor radiotherapy.Hereditas · 2020Review
- Cucurbitacin B and I inhibits colon cancer growth by targeting the Notch signaling pathway.Scientific reports · 2020Article
- Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine.Chinese medicine · 2019Review
- Camptothecin induces GOncotarget · 2018Article
Corrections and comments
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cucurbitacins are a class of triterpenoids widely distributed in plant kingdom with potent anti-cancer activities both in vitro and in vivo by inducing cycle arrest, autophagy, and apoptosis. Cucurbitacin B (Cuc B), could induce S or G2/M cell cycle arrest in cancer cells while the detailed mechanisms remain to be clear. This study was designed to precisely dissect the signaling pathway(s) responsible for Cuc B induced cell cycle arrest in human lung adenocarcinoma epithelial A549 cells. We demonstrated that low concentrations of Cuc B dramatically induced G2/M phase arrest in A549 cells. Cuc B treatment caused DNA double-strand breaks (DSBs) without affecting the signal transducer and activator of transcription 3 (STAT3), the potential molecular target for Cuc B. Cuc B triggers ATM-activated Chk1-Cdc25C-Cdk1, which could be reversed by both ATM siRNA and Chk1 siRNA. Cuc B also triggers ATM-activated p53-14-3-3-σ pathways, which could be reversed by ATM siRNA. Cuc B treatment also led to increased intracellular reactive oxygen species (ROS) formation, which was inhibited by N-acetyl-l-cysteine (NAC) pretreatment. Furthermore, NAC pretreatment inhibited Cuc B induced DNA damage and G2/M phase arrest. Taken together, these results suggested that Cuc B induces DNA damage in A549 cells mediated by increasing intracellular ROS formation, which lead to G2/M cell phase arrest through ATM-activated Chk1-Cdc25C-Cdk1 and p53-14-3-3-σ parallel branches. These observations provide novel mechanisms and potential targets for better understanding of the anti-cancer mechanisms of cucurbitacins.
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