ArticleCell death & disease2019
The natural compound gracillin exerts potent antitumor activity by targeting mitochondrial complex II.
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 67 citations in OpenAlex.
- Gracillin overcomes osimertinib resistance in NSCLC via dual inhibition of EGFR and Mcl-1.Cancer gene therapy · 2026Article
- Study on the anti-lung cancer effects of Gracillin from Reineckia carnea by targeting STC1.BMC cancer · 2026Article
- A facile and practical method for the synthesis ofBeilstein journal of organic chemistry · 2026Article
- Modulation of the PI3K/Akt signaling pathway by steroidal saponins: therapeutic implications in cancer.Frontiers in pharmacology · 2026Review
- Antitumor natural products targeting mitochondrial NADH: ubiquinone oxidoreductase (complex I): a review.Frontiers in pharmacology · 2026Review
- Current status of traditional Chinese medicine in modulating mitochondrial metabolic abnormalities in tumors.Cancer biology & medicine · 2025Review
- Targeting the Mitochondria in High-Grade Gliomas.Cancers · 2025Review
- Gracillin suppresses cancer progression through inducing Merlin/LATS protein-protein interaction and activating Hippo signaling pathway.Acta pharmacologica Sinica · 2025Article
- 5-Bromouracil-gracillin (5BrU-G) complex: an APOBEC3-activated therapeutic strategy exploiting cancer-specific enzymatic activity for selective cytotoxicity.Medical oncology (Northwood, London, England) · 2025Article
- Gracillin Protects Liver Ischemia-Reperfusion Injury from Oxidative Stress-Induced Apoptosis.Drug design, development and therapy · 2025Article
- Article
- UHPLC-Q-TOF/MS unveils metabolic diversity inFrontiers in pharmacology · 2025Article
- Study on the mechanism of gracillin inhibiting theJournal of Cancer · 2025Article
- Natural Anticancer Drugs: Efficacy, Safety, and Future Challenges.Current medicinal chemistry · 2025Review
- Bushen Zhuyun Decoction Improves Endometrial Receptivity by Inhibiting NF-κB/NLRP3 Signaling Pathway.Combinatorial chemistry & high throughput screening · 2025Article
- Honey Targets Ribosome Biogenesis Components to Suppress the Growth of Human Pancreatic Cancer Cells.Cancers · 2024Article
- The role ofHeliyon · 2024Review
- Review
- Semisynthesis and anti-cancer properties of novel honokiol derivatives in human nasopharyngeal carcinoma CNE-2Z cells.Journal of enzyme inhibition and medicinal chemistry · 2023Article
- A Comparative Analysis of Neuroprotective Properties of Taxifolin and Its Water-Soluble Form in Ischemia of Cerebral Cortical Cells of the Mouse.International journal of molecular sciences · 2023Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mitochondria play a pivotal role in cancer bioenergetics and are considered a potential target for anticancer therapy. Considering the limited efficacy and toxicity of currently available mitochondria-targeting agents, it is necessary to develop effective mitochondria-targeting anticancer drugs. By screening a large chemical library consisting of natural products with diverse chemical entities, we identified gracillin, a steroidal saponin, as a mitochondria-targeting antitumor drug. Gracillin displayed broad-spectrum inhibitory effects on the viability of a large panel of human cancer cell lines, including those carrying acquired resistance to chemotherapy or EGFR-targeting drugs, by inducing apoptosis. We show that gracillin attenuates mitochondria-mediated cellular bioenergetics by suppressing ATP synthesis and by producing reactive oxygen species (ROS). Mechanistically, gracillin disrupts complex II (CII) function by abrogating succinate dehydrogenase (SDH) activity without affecting the succinate:ubiquinone reductase. The gracillin-induced cell death was potentiated by 3-nitropropionic acid (3-NPA) or thenoyltrifluoroacetone (TTFA), which inhibit CII by binding to the active site of SDHA or to the ubiquinone-binding site, respectively. Finally, we show that gracillin effectively suppressed the mutant-Kras-driven lung tumorigenesis and the growth of xenograft tumors derived from cell lines or patient tissues. Gracillin displayed no obvious pathophysiological features in mice. Collectively, gracillin has potential as a CII-targeting antitumor drug.
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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.