ArticleActa pharmacologica Sinica2009
LGH00031, a novel ortho-quinonoid inhibitor of cell division cycle 25B, inhibits human cancer cells via ROS generation.
Article in Acta pharmacologica Sinica, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 23 citations in OpenAlex.
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- Recent advances and future directions in etiopathogenesis and mechanisms of reactive oxygen species in cancer treatment.Pathology oncology research : POR · 2023Review
- Dual Role of Reactive Oxygen Species and their Application in Cancer Therapy.Journal of Cancer · 2021Review
- Review
- Shikonin inhibits cancer cell cycling by targeting Cdc25s.BMC cancer · 2019Article
- Targeting Cyclin-Dependent Kinases for Treatment of Gynecologic Cancers.Frontiers in oncology · 2018Review
- Phosphatases and kinases regulating CDC25 activity in the cell cycle: clinical implications of CDC25 overexpression and potential treatment strategies.Molecular and cellular biochemistry · 2016Review
- Article
- Insights into the distinguishing stress-induced cytotoxicity of chiral gold nanoclusters and the relationship with GSTP1.Theranostics · 2015Article
- Therapeutic targeting the cell division cycle 25 (CDC25) phosphatases in human acute myeloid leukemia--the possibility to target several kinases through inhibition of the various CDC25 isoforms.Molecules (Basel, Switzerland) · 2014Review
- Dual-Specificity Phosphatase CDC25A/B Inhibitor Identified from a Focused Library with Nonelectrophilic Core Structure.ACS medicinal chemistry letters · 2012Article
- Novel microtubule-targeted agent 6-chloro-4-(methoxyphenyl) coumarin induces G2-M arrest and apoptosis in HeLa cells.Acta pharmacologica Sinica · 2012Article
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
aimTo discover novel cell division cycle 25 (CDC25) B inhibitors and elucidate the mechanisms of inhibition in cancer cells.
methodsCell growth inhibition was detected by MTT assay, the cell cycle was analyzed by flow cytometry, and protein expression and phosphorylation was examined by Western blot analysis.
resultsLGH00031 inhibited CDC25B irreversibly in vitro in a dose-dependent manner, and impaired the proliferation of tumor cell lines. In synchronized HeLa cells, LGH00031 delayed the cell cycle progression at the G(2)/M phase. LGH00031 increased cyclin-dependent kinase 1 (CDK1) tyrosine 15 phosphorylation and cyclin B1 protein level. The activity of LGH00031 against CDC25B in vitro relied on the existence of 1,4-dithiothreitol (DTT) or dihydrolipoic acid and oxygen. The oxygen free radical scavenger catalase and superoxide dismutase reduced the inactivation of CDC25 by LGH00031, confirming that reactive oxygen species (ROS) mediate the inactivation process in vitro. LGH00031 accelerated cellular ROS production in a dose-dependent manner, and N-acetyl cysteine (NAC) markedly decreased the ROS production induced by LGH00031. Correspondingly, the LGH00031-induced decrease in cell viability and cell cycle arrest, cyclin B1 protein level, and phosphorylation of CDK1 tyrosine 15 were also rescued by NAC that decreased ROS production.
conclusionThe activity of LGH00031 at the molecular and cellular level is mediated by ROS.
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