acetyl-aspartyl-glutamyl-valyl-aspartal and Lung-Neoplasms

1. 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. 2. During apoptosis, an increase in cytochrome c of cytosolic fraction and activation of caspase-3, identified by the cleavage of its proform, were observed. 3. 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. 4. 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. 5. The decrease in the expression of PKC delta and epsilon may play a critical role in aloe-emodin- and emodin-induced apoptosis in CH27 and H460 cells. 6. The present study also demonstrated that PKC stimulation occurs at a site downstream of caspase-3 in the emodin-mediated apoptotic pathway.

Topics: Anthraquinones; Antineoplastic Agents; Apoptosis; Blotting, Western; Caspase 3; Caspases; Cell Survival; Cytochrome c Group; DNA; DNA Fragmentation; Dose-Response Relationship, Drug; Emodin; Enzyme Activation; Enzyme Inhibitors; Flow Cytometry; Humans; Isoenzymes; Lung Neoplasms; Oligopeptides; Protein Kinase C; Time Factors; Tumor Cells, Cultured

Our objective was to determine whether paclitaxel-induced apoptosis in human lung cancer cells is Fas dependent.. Human lung cancer cell lines were evaluated for morphologic evidence of apoptosis, DNA fragmentation (TUNEL positivity), and caspase-3 activation after paclitaxel treatment. Human lung adenocarcinoma, squamous cell carcinoma, undifferentiated lung carcinoma, and bronchoalveolar carcinoma cell lines were each cultured in 10 micromol/L paclitaxel.. After 24 hours of culture in paclitaxel, a 22% to 69% increase in the number of apoptotic cells was evident by means of methylene blue-azure A-eosin staining with characteristic blebbing and nuclear condensation. TUNEL assay also confirmed an increase of 19.9% to 73.0% of cells with nuclear fragmentation. Caspase-3 activity, assayed by Z-DEVD cleavage, increased from 20% to 215% (P <.05). ZB4, an antagonistic anti-Fas antibody, did not block paclitaxel induction of caspase-3 activity (155.8 vs 165.8 U, not significant). Apoptotic morphologic changes were inhibited in cells cultured in the presence of paclitaxel and Ac-DEVD-CHO, a caspase-3 inhibitor.. Paclitaxel induces apoptosis in lung cancer cell lines, as assessed by a consistent increase in caspase-3 activity, DNA laddering, and characteristic morphologic changes. Paclitaxel-induced apoptosis in human lung cancer cells is associated with caspase-3 activation but is not Fas dependent.

Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Carcinoma, Non-Small-Cell Lung; Caspase 3; Caspase Inhibitors; Caspases; DNA Fragmentation; fas Receptor; Humans; In Situ Nick-End Labeling; Lung Neoplasms; Oligopeptides; Paclitaxel; Tumor Cells, Cultured

In our previous studies (S. Simizu, et al., 1996, Cancer Res. 56, 4978-4982), we reported that apoptosis of human small cell lung carcinoma (SCLC) cells induced by protein tyrosine kinase inhibitors, such as erbstatin and herbimycin A, was mediated by H2O2 via a newly synthesized protein(s). In the present study, we demonstrated that induction of apoptosis by erbstatin resulted in activation of caspase-3(-like) proteases, which are interleukin-1 beta-converting enzyme family proteases (caspases) and that inhibition of these protease activities reduced the extent of cell death and H2O2 generation. We also demonstrated that expression of apoptotic protein Bax was induced by erbstatin. Erbstatin-induced Bax expression was inhibited by the inhibitor of caspase-3(-like) proteases. These results indicate that generation of intracellular H2O2 and Bax expression in tyrosine kinase inhibitor-induced apoptosis were modulated by the activation of caspase-3(-like) proteases in SCLC cells.

Topics: Apoptosis; bcl-2-Associated X Protein; Benzoquinones; Carcinoma, Small Cell; Caspase 3; Caspases; Cysteine Endopeptidases; Cysteine Proteinase Inhibitors; Enzyme Activation; Enzyme Inhibitors; Enzyme Precursors; Humans; Hydrogen Peroxide; Hydroquinones; Kinetics; Lactams, Macrocyclic; Lung Neoplasms; Oligopeptides; Protein-Tyrosine Kinases; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcl-2; Quinones; Rifabutin; Tumor Cells, Cultured

Vinblastine arrests cells in the G2/M phase of the cell cycle and subsequently induces cell death by apoptosis. We found that treatment of cells with vinblastine induced phosphorylation of Bcl-2, resulting in the dissociation of Bcl-2 and Bax. Moreover, vinblastine-induced apoptosis was suppressed by an inhibitor of caspase-3, Ac-DEVD-CHO; and a 17-kDa active fragment of caspase-3 was detected following vinblastine treatment, suggesting that caspase-3 is involved in vinblastine-induced apoptosis. However, Ac-DEVD-CHO affected neither vinblastine-induced Bcl-2 phosphorylation nor vinblastine-induced G2/M arrest. Vinblastine caused G2/M arrest prior to apoptosis, whereas vinblastine-induced apoptosis was not dependent on the duration of the G2/M phase. Thus, vinblastine-induced apoptosis might be mediated by the phosphorylation of Bcl-2, resulting in Bcl-2 inactivation, and by subsequent activation of caspase-3.

Topics: Apoptosis; Carcinoma, Small Cell; Caspase 3; Caspases; Cysteine Proteinase Inhibitors; Enzyme Activation; G2 Phase; Humans; Lung Neoplasms; Mitosis; Oligopeptides; Peptide Fragments; Phosphorylation; Proto-Oncogene Proteins c-bcl-2; Tumor Cells, Cultured; Vinblastine