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Your search keyword '"Harringtonines toxicity"' showing total 2 results
Start Over Descriptor "Harringtonines toxicity" Publisher nature publishing group
2 results on '"Harringtonines toxicity"'

1. Homoharringtonine induces apoptosis and inhibits STAT3 via IL-6/JAK1/STAT3 signal pathway in Gefitinib-resistant lung cancer cells.

Author

Cao W, Liu Y, Zhang R, Zhang B, Wang T, Zhu X, Mei L, Chen H, Zhang H, Ming P, and Huang L

Subjects
Animals, Antineoplastic Agents chemistry, Antineoplastic Agents therapeutic use, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung metabolism, Carcinoma, Non-Small-Cell Lung pathology, Cell Line, Tumor, Cell Survival drug effects, Docetaxel, Drug Synergism, Enzyme-Linked Immunosorbent Assay, ErbB Receptors genetics, ErbB Receptors metabolism, Gefitinib, Harringtonines chemistry, Harringtonines therapeutic use, Homoharringtonine, Humans, Interleukin-6 analysis, Interleukin-6 metabolism, Janus Kinase 1 metabolism, Lung Neoplasms drug therapy, Lung Neoplasms metabolism, Lung Neoplasms pathology, Male, Mice, Mice, Nude, Mitochondria drug effects, Mitochondria metabolism, Phosphorylation drug effects, STAT3 Transcription Factor metabolism, Taxoids therapeutic use, Taxoids toxicity, Transplantation, Heterologous, Antineoplastic Agents toxicity, Apoptosis drug effects, Drug Resistance, Neoplasm drug effects, Harringtonines toxicity, Quinazolines toxicity, Signal Transduction drug effects
Abstract

Tyrosine kinase inhibitors (TKIs) are mostly used in non-small cell lung cancer (NSCLC) treatment. Unfortunately, treatment with Gefitinib for a period of time will result in drug resistance and cause treatment failure in clinic. Therefore, exploring novel compounds to overcome this resistance is urgently required. Here we investigated the antitumor effect of homoharringtonine (HHT), a natural compound extracted from Cephalotaxus harringtonia, on Gefitinib-resistant NSCLC cell lines in vitro and in vivo. NCI-H1975 cells with EGFR T790M mutation are more sensitive to HHT treatment compared with that of A549 cells with wild type EGFR. HHT inhibited cells growth, cell viability and colony formation, as well as induced cell apoptosis through mitochondria pathway. Furthermore, we explored the mechanism of HHT inhibition on NSCLC cells. Higher level of interleukin-6 (IL-6) existed in lung cancer patients and mutant EGFR and TGFβ signal requires the upregulation of IL-6 through the gp130/JAK pathway to overactive STAT3, an oncogenic protein which has been considered as a potential target for cancer therapy. HHT reversiblely inhibited IL-6-induced STAT3 Tyrosine 705 phosphorylation and reduced anti-apoptotic proteins expression. Gefitinib-resistant NSCLC xenograft tests also confirmed the antitumor effect of HHT in vivo. Consequently, HHT has the potential in Gefitinib-resistant NSCLC treatment.

Published
2015
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2. Homoharringtonine acts synergistically with SG235-TRAIL, a conditionally replicating adenovirus, in human leukemia cell lines.

Author

Meng HT, Li L, Liu H, Wang Y, Li GC, and Qian WB

Subjects
Adenoviridae metabolism, Antineoplastic Agents, Phytogenic toxicity, Apoptosis drug effects, Blotting, Western, Caspase 3 metabolism, Caspase 9 metabolism, Cell Line, Tumor, Combined Modality Therapy, Flow Cytometry, Harringtonines toxicity, Homoharringtonine, Humans, Leukocytes, Mononuclear drug effects, Mesenchymal Stem Cells drug effects, Oncolytic Viruses metabolism, TNF-Related Apoptosis-Inducing Ligand administration & dosage, Antineoplastic Agents, Phytogenic pharmacology, Harringtonines pharmacology, Leukemia drug therapy, Oncolytic Virotherapy methods
Abstract

Aim: To investigate the synergistic effects of SG235-TRAIL, a novel oncolytic adenovirus expressing tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and homoharringtonine (HHT) in human leukemia cell lines., Methods: The combined effect of SG235-TRAIL and HHT was assessed using a crystal violet assay and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, followed by combination index analysis. Cell apoptosis was measured using flow cytometry combined with fluorescein-isothiocyanate-Annexin V staining. The activation of caspase pathway and the expression of Bcl-2 family proteins, TRAIL, and E1A were examined using Western blotting., Results: HHT synergized the cytotoxicity of SG235-TRAIL against leukemia cell lines Kasumi-1, KG-1, HL-60, and U937, concomitantly with increased apoptosis and enhanced activity of caspase-3 and -9. The combination therapy resulted in significantly lower levels of Bcl-2, Mcl-1, and Bid compared to treatment of cells with either HHT or SG235-TRAIL alone, suggesting that HHT sensitizes leukemia cells to SG235-TRAIL virus through alteration of anti-apoptotic signaling elements. Importantly, HHT combined with SG235-TRAIL did not show significant cytotoxicity to normal human mononuclear cells and mesenchymal stem cells., Conclusion: Combining oncolytic adenovirus SG235-TRAIL and HHT synergistically enhances cytotoxicity in leukemia cells in vitro, suggesting that the combination therapy could represent a rational approach for the treatment of leukemia.

Published
2009
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