ArticleJournal of hematology & oncology2017
Augmentation of the anticancer activity of CYT997 in human prostate cancer by inhibiting Src activity.
Article in Journal of hematology & oncology, 2017. 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.
- Identification and validation of microtubule depolymerizing agent, CYT997, as a potential drug candidate for hepatocellular carcinoma.Liver international : official journal of the International Association for the Study of the Liver · 2023Article
- Receptor tyrosine kinase-like orphan receptor 1 inhibitor strictinin exhibits anti-cancer properties against highly aggressive androgen-independent prostate cancer.Exploration of targeted anti-tumor therapy · 2023Article
- FGF19/FGFR4 signaling axis confines and switches the role of melatonin in head and neck cancer metastasis.Journal of experimental & clinical cancer research : CR · 2021Article
- Mitochondrial ROS accumulation inhibiting JAK2/STAT3 pathway is a critical modulator of CYT997-induced autophagy and apoptosis in gastric cancer.Journal of experimental & clinical cancer research : CR · 2020Article
- Src Family Kinases as Therapeutic Targets in Advanced Solid Tumors: What We Have Learned so Far.Cancers · 2020Review
- Targeting the Extra-Cellular Matrix-Tumor Cell Crosstalk for Anti-Cancer Therapy: Emerging Alternatives to Integrin Inhibitors.Frontiers in oncology · 2020Review
- Nck-associated protein 1 associates with HSP90 to drive metastasis in human non-small-cell lung cancer.Journal of experimental & clinical cancer research : CR · 2019Article
- Intracellular reduction in ATP levels contributes to CYT997-induced suppression of metastasis of head and neck squamous carcinoma.Journal of cellular and molecular medicine · 2019Article
- CYT997(Lexibulin) induces apoptosis and autophagy through the activation of mutually reinforced ER stress and ROS in osteosarcoma.Journal of experimental & clinical cancer research : CR · 2019Article
- Lipoxin A4 Ameliorates Acute Pancreatitis-Associated Acute Lung Injury through the Antioxidative and Anti-Inflammatory Effects of the Nrf2 Pathway.Oxidative medicine and cellular longevity · 2019Article
- Autophagy blockade sensitizes human head and neck squamous cell carcinoma towards CYT997 through enhancing excessively high reactive oxygen species-induced apoptosis.Journal of molecular medicine (Berlin, Germany) · 2018Article
- Combating head and neck cancer metastases by targeting Src using multifunctional nanoparticle-based saracatinib.Journal of hematology & oncology · 2018Article
- Implications of FGF19 on sorafenib-mediated nitric oxide production in hepatocellular carcinoma cells - a short report.Cellular oncology (Dordrecht, Netherlands) · 2018Article
- Combined targeting of Arf1 and Ras potentiates anticancer activity for prostate cancer therapeutics.Journal of experimental & clinical cancer research : CR · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAbnormalities of tubulin polymerization and microtubule assembly are often seen in cancer, which make them very suitable targets for the development of therapeutic approach against rapidly dividing and aggressive cancer cells. CYT997 is a novel microtubule-disrupting agent with anticancer activity in multiple cancer types including prostate cancer. However, the molecular mechanisms of action of CYT997 in prostate cancer have not been well characterized.
methodsSrc knockdown cells were achieved by lentiviral-mediated interference. The drug effects on cell proliferation were measured by MTS. The drug effects on cell viability and death were determined by Cell Titer-Glo® Luminescent cell viability kit and flow cytometry with Zombie Aqua™ staining. The drug effects on apoptosis were assessed by Cell Death Detection Elisa kit and Western blot with a cleaved PARP antibody. The drug effects on cell invasion were examined by Matrigel-coated Boyden chambers. Oxidative stress was detected by DCFH-DA staining and electrochemical biosensor. Mouse models generated by subcutaneous or intracardiac injection were used to investigate the in vivo drug efficacy in tumor growth and metastasis.
resultsCYT997 effectively inhibited proliferation, survival, and invasion of prostate cancer cells via blocking multiple oncogenic signaling cascades but not the Src pathway. Inhibition of Src expression by small hairpin RNA or inactivation of Src by dasatinib increased the CYT997-induced cytotoxicity of in vitro. Moreover, the combination of dasatinib and CYT997 exhibited a superior inhibitory effect on tumor growth and metastasis compared with either of the drugs alone.
conclusionOur findings demonstrate that blockage of Src augments the anticancer effect of CYT997 on prostate cancer and suggest that co-treatment of dasatinib and CYT997 may represent an effective therapeutic regimen for limiting prostate cancer.
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