ArticleBMC cancer2011
Cucurbitacin-I (JSI-124) activates the JNK/c-Jun signaling pathway independent of apoptosis and cell cycle arrest in B leukemic cells.
Article in BMC cancer, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 28 citations in OpenAlex.
- JSI-124 Induces Cell Cycle Arrest and Regulates the Apoptosis in Glioblastoma Cells.Biomedicines · 2023Article
- Modulation of Cytoskeleton, Protein Trafficking, and Signaling Pathways by Metabolites fromPharmaceuticals (Basel, Switzerland) · 2022Review
- Perspectives on natural compounds in chemoprevention and treatment of cancer: an update with new promising compounds.European journal of cancer (Oxford, England : 1990) · 2021Review
- Secalonic acid D induces cell apoptosis in both sensitive and ABCG2-overexpressing multidrug resistant cancer cells through upregulating c-Jun expression.Acta pharmaceutica Sinica. B · 2019Article
- Cell Cycle Arrest and Apoptosis Induced by Porphyromonas gingivalis Require Jun N-Terminal Protein Kinase- and p53-Mediated p38 Activation in Human Trophoblasts.Infection and immunity · 2018Article
- The cucurbitacins D, E, and I fromIranian journal of basic medical sciences · 2018Article
- Cucurbitacin-I inhibits Aurora kinase A, Aurora kinase B and survivin, induces defects in cell cycle progression and promotes ABT-737-induced cell death in a caspase-independent manner in malignant human glioma cells.Cancer biology & therapy · 2015Article
- JSI124 inhibits breast cancer cell growth by suppressing the function of B cells via the downregulation of signal transducer and activator of transcription 3.Oncology letters · 2014Article
- Cucurbitacin E induces cell cycle G2/M phase arrest and apoptosis in triple negative breast cancer.PloS one · 2014Article
- Activation of the NF-κB pathway by the STAT3 inhibitor JSI-124 in human glioblastoma cells.Molecular cancer research : MCR · 2013Article
- Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCucurbitacin-I (JSI-124) is potent inhibitor of JAK/STAT3 signaling pathway and has anti-tumor activity in a variety of cancer including B cell leukemia. However, other molecular targets of JSI-124 beyond the JAK/STAT3 pathway are not fully understood.
methodsBJAB, I-83, NALM-6 and primary CLL cells were treated with JSI-124 as indicated. Apoptosis was measured using flow cytometry for accumulation of sub-G1 phase cells (indicator of apoptosis) and Annexin V/PI staining. Cell cycle was analyzed by FACS for DNA content of G1 and G2 phases. Changes in phosphorylation and protein expression of p38, Erk1/2, JNK, c-Jun, and XIAP were detected by Western blot analysis. STAT3 and c-Jun genes were knocked out using siRNA transfection. VEGF expression was determined by mRNA and protein levels by RT-PCR and western blotting. Streptavidin Pull-Down Assay was used to determine c-Jun binding to the AP-1 DNA binding site.
resultsHerein, we show that JSI-124 activates c-Jun N-terminal kinase (JNK) and increases both the expression and serine phosphorylation of c-Jun protein in the B leukemic cell lines BJAB, I-83 and NALM-6. JSI-124 also activated MAPK p38 and MAPK Erk1/2 albeit at lower levels than JNK activation. Inhibition of the JNK signaling pathway failed to effect cell cycle arrest or apoptosis induced by JSI-124 but repressed JSI-124 induced c-Jun expression in these leukemia cells. The JNK pathway activation c-Jun leads to transcriptional activation of many genes. Treatment of BJAB, I-83, and NALM-6 cells with JSI-124 lead to an increase of Vascular Endothelial Growth Factor (VEGF) at both the mRNA and protein level. Knockdown of c-Jun expression and inhibition of JNK activation significantly blocked JSI-124 induced VEGF expression. Pretreatment with recombinant VEGF reduced JSI-124 induced apoptosis.
conclusionsTaken together, our data demonstrates that JSI-124 activates the JNK signaling pathway independent of apoptosis and cell cycle arrest, leading to increased VEGF expression.
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