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H460 Cells (h460 + cell)
Selected AbstractsEnhanced cytotoxicity induced by gefitinib and specific inhibitors of the Ras or phosphatidyl inositol-3 kinase pathways in non-small cell lung cancer cellsINTERNATIONAL JOURNAL OF CANCER, Issue 1 2006Maarten L. Janmaat Abstract In this study, we have characterized a panel of NSCLC cell lines with differential sensitivity to gefitinib for activating mutations in egfr, pik3ca, and k-ras, and basal protein expression levels of PTEN. The egfr mutant NSCLC cell line H1650 as well as the egfr wild type cell lines H292 and A431 were highly sensitive to gefitinib treatment, indicating that other factors determine gefitinib-sensitivity in egfr wild type cells. Activating k-ras mutations were specifically detected in gefitinib-resistant cells, suggesting that the occurrence of k-ras mutations is correlated with resistance to EGFR antagonists. No pik3ca mutations were detected within the panel of cell lines, and PTEN protein expression levels did not correlate with gefitinib sensitivity. Gefitinib effectively blocked Akt and Erk phosphorylation in two gefitinib-sensitive NSCLC cell lines, further supporting our previous findings that persistent activity of the PI3K/Akt and/or Ras/Erk pathways is associated with gefitinib-resistance of NSCLC cell lines. Gefitinib-resistant NSCLC cell lines, showing EGFR-independent activity of the PI3K/Akt or Ras/Erk pathways, were treated with gefitinib in combination with specific inhibitors of mTOR, P13K, Ras, and MEK. Additive cytotoxicity was observed in A549 cells co-treated with gefitinib and the MEK inhibitor U0126 or the farnesyl transferase inhibitor SCH66336 and in H460 cells treated with gefitinib and the PI3K inhibitor LY294002, but not in H460 cells treated with gefitinib and rapamycin. These data suggest that combination treatment of NSCLC cells with gefitinib and specific inhibitors of the PI3K/Akt and Ras/Erk pathways may provide a successful strategy. © 2005 Wiley-Liss, Inc. [source] Release of nucleophosmin from the nucleus: Involvement in aloe-emodin,induced human lung non small carcinoma cell apoptosisINTERNATIONAL JOURNAL OF CANCER, Issue 6 2005Hong-Zin Lee Abstract Aloe-emodin (1,8-dihydroxy-3-(hydroxymethyl)-anthraquinone) is one of the active constituents from the root and rhizome of Rheum palmatum. Our previous study has demonstrated that aloe-emodin induced a significant change in the expression of lung cancer cell apoptosis-related proteins compared to those of control cells. However, the molecular mechanisms underlying the biological effects of aloe-emodin still remain unknown. Based on these reasons, we were interested in the change of aloe-emodin,induced total protein expression by the proteomics technique during aloe-emodin,induced lung cancer cell apoptosis. Our study applied 2D electrophoresis to analyze the proteins involved in aloe-emodin,induced apoptosis in H460 cells. We found that the release of nucleophosmin from the nucleus to the cytosol and the degradation of nucleophosmin were associated with aloe-emodin,induced H460 cell apoptosis. Our study also demonstrated that the gene expression of nucleophosmin remained unchanged after treatment with aloe-emodin. The aloe-emodin,caused increase in the amount of proform and fragment of nucleophosmin in cytoplasm may be one of the important events for aloe-emodin,induced H460 cell apoptosis. © 2004 Wiley-Liss, Inc. [source] Involvement of calcium in the differential induction of heat shock protein 70 by heat shock protein 90 inhibitors, geldanamycin and radicicol, in human non-small cell lung cancer H460 cellsJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 1 2006Yuo-Sheng Chang Abstract Both geldanamycin (GA) and radicicol (RA) are HSP90 binding agents that possess antitumour activities. Although the in vitro data indicated that the inhibitory constant of RA is much bigger than that of GA, the in vivo data on drug efficacy might reveal different results. We have recently shown that treatment with GA induces a heat-shock response and that calcium mobilization may be involved in the process. By using induction of HSP70 as the endpoint assay, we found changes in upstream signaling mediators, including HSF1 and calcium mobilization, as well as possible involvement of protein kinase in human non-small cell lung cancer H460 cells treated with GA and RA. Our results demonstrated that calcium mobilization, a calcium dependent and H7-sensitive protein kinase, along with HSF1 activation by phosphorylation, are all involved in the HSP70 induction process triggered by the drugs. However, only GA, but not RA, can provoke a rapid calcium mobilization and thereby result in an instant induction of HSP70. Furthermore, the rapid calcium influx, followed by instant HSP induction, could be achieved in GA- or RA-treated cells placed in a medium containing excessive calcium while the response was completely abolished in cells depleted of calcium. Taken together, our findings suggest that differential calcium signaling may account for the differential induction of HSP and the action of GA and RA. J. Cell. Biochem. © 2005 Wiley-Liss, Inc. [source] Monodemethylated polymethoxyflavones from sweet orange (Citrus sinensis) peel Inhibit growth of human lung cancer cells by apoptosisMOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 3 2009Hang Xiao Abstract Polymethoxyflavones (PMFs) are almost exclusively found in the Citrus genus, particularly in the peels of sweet orange (Citrus sinensis L. Osbeck) and mandarin (C. reticulate Blanco). We studied the effects of two major PMFs, namely, nobiletin and 3,5,6,7,8,3,,4,-heptamethoxyflavone (HMF), and two major monodemethylated PMFs, namely 5-hydroxy-3,7,8,3,,4,-pentamethoxyflavone (5HPMF), and 5-hydroxy-3,6,7,8,3,,4,-hexamethoxyflavone (5HHMF), on the growth of human lung cancer H1299, H441, and H460 cells. Monodemethylated PMFs were much more potent in growth inhibition of lung cancer cells than their permethoxylated counterpart PMFs. In H1299 cells, cell cycle analyses further revealed that monodemethylated PMFs caused significant increase in sub-G0/G1 phase, suggesting possible role of apoptosis in the growth inhibition observed, whereas the permethoxylated counterpart PMFs did not affect cell cycle distribution at same concentrations tested. These results strongly suggested that the phenolic group is essential for the growth inhibitory activity of monodemethylated PMFs. Further studies in H1299 cells demonstrated that monodemethylated PMFs downregulated oncogenic proteins, such as iNOS, COX-2, Mcl-1, and K-ras, as well as induced apoptosis evidenced by activation of caspase-3 and cleavage of PARP. Our results provide rationale to develop orange peel extract enriched with monodemethylated PMFs into value-added nutraceutical products for cancer prevention. [source] Protein kinase C involvement in aloe-emodin- and emodin-induced apoptosis in lung carcinoma cellBRITISH JOURNAL OF PHARMACOLOGY, Issue 5 2001Hong-Zin Lee This study demonstrated aloe-emodin- and emodin-induced apoptosis in lung carcinoma cell lines CH27 (human lung squamous carcinoma cell) and H460 (human lung non-small cell carcinoma cell). Aloe-emodin- and emodin-induced apoptosis was characterized by nuclear morphological changes and DNA fragmentation. During apoptosis, an increase in cytochrome c of cytosolic fraction and activation of caspase-3, identified by the cleavage of its proform, were observed. To elucidate whether the expression of protein kinase C (PKC) isozymes are involved in aloe-emodin- and emodin-induced apoptosis, this study examined the changes of PKC isozymes by Western blotting techniques during aloe-emodin- and emodin-induced apoptosis. The expression of PKC isozymes involved in aloe-emodin- and emodin-induced apoptosis of CH27 and H460 cells. In this study, aloe-emodin and emodin induced the changes of each of PKC isozymes in CH27 and H460 cells. The decrease in the expression of PKC, and , may play a critical role in aloe-emodin- and emodin-induced apoptosis in CH27 and H460 cells. The present study also demonstrated that PKC stimulation occurs at a site downstream of caspase-3 in the emodin-mediated apoptotic pathway. British Journal of Pharmacology (2001) 134, 1093,1103; doi:10.1038/sj.bjp.0704342 [source] | |||||||||||||