artonin-e and Lung-Neoplasms

Knowledge regarding substances that attenuate motility of cancer cells has gathered significant attention, as they benefit the development of novel anticancer strategies. The anti-migration and anti-invasion activities of artonin E, extracted from bark of Artocarpus gomezianus, were investigated in lung cancer cells in this study.. Cytotoxicity and antiproliferative effects of artonin E were examined by 3- (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Migration and invasion assays were performed on H460, H23, A549 and H292 human lung cancer cells. Cell morphology was determined by phalloidin-rhodamine staining. Motility-related proteins were investigated by western blotting.. Artonin E exhibited anti-migration and anti-invasion activities in H460 cells. Cell morphology revealed that treatment of the cells with non-toxic concentrations of artonin E resulted in a decrease of activated focal adhesion kinase (FAK), downstream protein kinase B (AKT) activation, and Cell division cycle-42 (CDC42), all of which were associated with the anti-motility effect of this compound. Artonin E inhibited invasion and migration of other lung cancer cells, namely H292, H23 and A549 cells.. These results suggest that artonin E may be a promising candidate for anti-metastasis use.

Topics: Carcinoma, Non-Small-Cell Lung; Caveolin 1; cdc42 GTP-Binding Protein; Cell Death; Cell Line, Tumor; Cell Movement; Cell Survival; Flavonoids; Focal Adhesion Protein-Tyrosine Kinases; Humans; Lung Neoplasms; Neoplasm Invasiveness; Proto-Oncogene Proteins c-akt; Pseudopodia; Signal Transduction

Anoikis, or detachment-induced apoptosis, is recognized as a key inhibitory process of cancer metastasis. Since lung cancer cells possess an ability to resist anoikis, resulting in a high rate of metastasis and death, the present study aimed to investigate the possible anoikis-sensitizing effect of artonin E (AE).. AE was extracted from bark of Artocarpus gomezianus. Anoikis sensitization of AE was investigated in H460, A549 and H292 human lung cancer cells. The level of anoikis-related proteins was determined by western blot analysis and viable cells were measured by the 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) method.. AE was shown to enhance anoikis of H460 cells in a dose-dependent manner. We investigated the underlying mechanisms of AE on anoikis sensitization and found that AE sensitized the cells by down-regulating the anti-apoptotic myeloid leukemia cell sequence-1 (MCL1) protein but had no significant effect on other proteins of the B-cell lymphoma-2 (BCL2) family, including BCL2 and BCL2-associated X protein (BAX). Anoikis sensitization of AE was consistently observed in A549 and H292 lung cancer cells.. The present study demonstrates a novel activity of AE on lung cancer cell anoikis for the first time which might lead to the development of a new strategy for lung cancer therapy.

Topics: Anoikis; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cell Survival; Down-Regulation; Flavonoids; Humans; Kidney; Lung Neoplasms; Myeloid Cell Leukemia Sequence 1 Protein; Proto-Oncogene Proteins c-bcl-2