Dehydrocostuslactone-induced apoptosis through oxidative and endoplasmic reticulum stress signaling in human non-small cell lung cancer cells
J. Y. Hung, Y. L. Hsu, W. C. Ni, Y. M. Tsai, C. J. Yang, M. S. Huang, P. L. Kuo (Taiwan)
Source: Annual Congress 2010 - Pathology of lung cancer
Session: Pathology of lung cancer
Session type: Thematic Poster Session
Number: 3266
Disease area: Thoracic oncology
Abstract Lung cancer is one of the leading causes of death in the world, and non-small cell lung carcinoma (NSCLC) accounts for approximately 75-85% of all lung cancers. Since current treatment modalities are inadequate, novel therapies are needed to reduce the increasing incidence of pulmonary neoplasms. This study investigates the anticancer effect of dehydrocostuslactone (DHE), a medicinal plant-derived sesquiterpene lactone, on human non-small cell lung cancer cell lines, A549 and NCI-H460. Our results show that DHE inhibits the proliferation of A549 and NCI-H460 cells. DHE induced apoptosis in both A549 and NCI-H460 cells. DHE triggered endoplasmic reticulum (ER) stress, as indicated by changes in cytosol-calcium levels, PKR-like ER kinase (PERK) phosphorylation, inositol requiring protein 1 (IRE1) and CHOP/GADD153 upregulation, X-box transcription factor-1 (XBP-1) mRNA splicing, and caspase-4 activation. The release of calcium triggered the production of ROS, which further enhances calcium overloading and subsequently activates p38, JNK and ERK1/2. Both IRE1 miRNA transfection and BAPTA-AM pretreatment inhibit DHE-mediated apoptosis, supporting the hypothesis that DHE induces cell death through ER stress. Importantly, a novel anticancer agent for the treatment of non-small cell lung cancer, and is supported by animal studies which have shown a dramatic 50% reduction in tumor size after 28 days of treatment. This study demonstrates that DHE may be a novel anticancer agent for the treatment of non-small cell lung cancer.
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J. Y. Hung, Y. L. Hsu, W. C. Ni, Y. M. Tsai, C. J. Yang, M. S. Huang, P. L. Kuo (Taiwan). Dehydrocostuslactone-induced apoptosis through oxidative and endoplasmic reticulum stress signaling in human non-small cell lung cancer cells. Eur Respir J 2010; 36: Suppl. 54, 3266
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