benzyloxycarbonylvalyl-alanyl-aspartyl-fluoromethyl-ketone and 7-hydroxystaurosporine

benzyloxycarbonylvalyl-alanyl-aspartyl-fluoromethyl-ketone has been researched along with 7-hydroxystaurosporine* in 2 studies

Other Studies

2 other study(ies) available for benzyloxycarbonylvalyl-alanyl-aspartyl-fluoromethyl-ketone and 7-hydroxystaurosporine

ArticleYear
Altered sensitivity of deoxyadenosine-resistant mouse leukemia L1210 cells to apoptosis induced by 7-hydroxystaurosporine.
    International journal of oncology, 2000, Volume: 17, Issue:4

    The deoxyadenosine-resistant mouse leukemia L1210 cell line (Y8) has previously been shown to be more sensitive to apoptosis induced by DNA damaging agents and by protein synthesis inhibitors than the parental wild-type L1210 (WT) cells. These responses occur independently of p53 as both cell lines lack wild-type p53 function. Recent evidence suggests that a serine/threonine kinase is involved in the divergent cellular responses of the WT and Y8 cells. In the present study, the effects of 7-hydroxystaurosporine (UCN-01), a relatively specific serine/threonine kinase inhibitor, were examined in the WT and Y8 cells. Both cell lines were equally sensitive to the growth inhibitory effects of UCN-01. However, the Y8 cells accumulated in G0/G1 and became apoptotic. Apoptosis induced by UCN-01 in the Y8 cells was mediated by a caspase-3-like activity which could be partially blocked by Ac-DEVD-CHO, a caspase-3 inhibitor. UCN-01 did not alter the phosphorylation status of cdc2 nor cyclin B1 and cdc2 protein levels in either cell line.

    Topics: Alkaloids; Amino Acid Chloromethyl Ketones; Animals; Apoptosis; Caspase 3; Caspase Inhibitors; Caspases; Cathepsins; CDC2 Protein Kinase; Cell Cycle; Coumarins; Cyclin B; Cyclin B1; Cysteine Proteinase Inhibitors; Cytochrome c Group; Deoxyadenosines; Dose-Response Relationship, Drug; Drug Resistance, Neoplasm; Enzyme Inhibitors; Flow Cytometry; Leukemia L1210; Mice; Oligopeptides; Protein Kinase C; Sensitivity and Specificity; Staurosporine; Tumor Cells, Cultured

2000
Activation of PKCalpha downstream from caspases during apoptosis induced by 7-hydroxystaurosporine or the topoisomerase inhibitors, camptothecin and etoposide, in human myeloid leukemia HL60 cells.
    The Journal of biological chemistry, 1997, Dec-12, Volume: 272, Issue:50

    We previously demonstrated that the anticancer agent and protein kinase C (PKC) inhibitor 7-hydroxystaurosporine (UCN-01) induces apoptosis independently of p53 and protein synthesis in HL60 cells. We now report the associated changes of PKC isoforms. PKCalpha, betaI, betaII, delta, and zeta activities were measured after immunoprecipitation of cytosols from UCN-01-treated HL60 cells. UCN-01 had no effect on PKCzeta and inhibited kinase activity of PKCbetaI, betaII, and delta. PKCalpha activity was initially inhibited at 1 h, and subsequently increased as cells underwent apoptosis 3 h after the beginning of UCN-01 treatment. Camptothecin (CPT) and etoposide (VP-16) also markedly enhanced PKCalpha activity during apoptosis in HL60 cells. However, CPT did not affect PKCbetaI, betaII and zeta, and activated PKCdelta. PKCalpha activation was not due to increased protein levels or proteolytic cleavage but was associated with PKCalpha autophosphorylation in vitro and increased phosphorylation in vivo. We also found that not only PKC delta but also PKC betaI was proteolytically activated in HL60 cells during apoptosis. The PKCalpha activation and hyperphosphorylation were abrogated by N-benzyloxycarbonyl-Val-Ala-Asp(O-methyl)-fluoromethylketone (z-VAD-fmk) under conditions that abrogated apoptosis. z-VAD-fmk also prevented PKCdelta and betaI proteolytic activation. Together these findings suggest that caspases regulate PKC activity during apoptosis in HL60 cells. At least two modes of activation were observed: hyperphosphorylation for PKCalpha and proteolytic activation for PKC delta and betaI.

    Topics: Alkaloids; Amino Acid Chloromethyl Ketones; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Apoptosis; Camptothecin; Cysteine Endopeptidases; Cysteine Proteinase Inhibitors; Enzyme Activation; Enzyme Inhibitors; Etoposide; HL-60 Cells; Humans; Isoenzymes; Protein Kinase C; Protein Kinase C-alpha; Staurosporine; Up-Regulation

1997