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Induction of tumor necrosis factor by bryostatin 1 is involved in synergistic interactions with paclitaxel in human myeloid leukemia cells.
Blood. 2003 May 01; 101(9):3648-57.Blood

Abstract

Interactions between the protein kinase C (PKC) activator/down-regulator bryostatin 1 and paclitaxel have been examined in human myeloid leukemia cells (U937) and in highly paclitaxel-resistant cells ectopically expressing a Bcl-2 phosphorylation loop-deleted protein (Delta Bcl-2). Treatment (24 hours) of wild-type cells with paclitaxel (eg, 5 to 20 nM) in combination with 10 nM bryostatin 1 induced a marked increase in mitochondrial damage (eg, cytochrome c and Smac/DIABLO [second mitochondria-derived activator of caspases/direct IAP binding protein with low pI] release), caspase activation, Bid cleavage, and apoptosis; moreover, bryostatin 1 circumvented the block to paclitaxel-induced mitochondrial injury and apoptosis conferred by ectopic expression of the loop-deleted protein. Coadministration of tumor necrosis factor (TNF) soluble receptors, or ectopic expression of CrmA or dominant-negative caspase-8, abrogated potentiation of paclitaxel-induced mitochondrial injury and apoptosis by bryostatin 1, implicating the extrinsic apoptotic pathway in this process. Similar events occurred in HL-60 leukemia cells. Potentiation of paclitaxel-induced apoptosis in wild-type and mutant cells by bryostatin 1 was associated with increases in TNF-alpha mRNA and protein and was mimicked by exogenous TNF-alpha. Coadministration of the selective PKC inhibitor GFX (1 microM) blocked the increase in TNF-alpha mRNA levels and apoptosis in bryostatin 1/paclitaxel-treated cells. Lastly, synchronization of cells in G(2)M increased their sensitivity to TNF-alpha-associated lethality. Collectively, these findings indicate that in U937 cells, bryostatin 1 promotes paclitaxel-mediated mitochondrial injury and apoptosis, and circumvents resistance to cell death conferred by loss of the Bcl-2 phosphorylation domain, through the PKC-dependent induction of TNF-alpha. They further suggest that this process is amplified by paclitaxel-mediated arrest of cells in G(2)M, where they are more susceptible to TNF-alpha-induced lethality.

Authors+Show Affiliations

Department of Biochemistry, Division of Hematology/Oncology, Virginia Commonwealth University/Medical College of Virginia, Richmond 23298, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

12522001

Citation

Wang, Shujie, et al. "Induction of Tumor Necrosis Factor By Bryostatin 1 Is Involved in Synergistic Interactions With Paclitaxel in Human Myeloid Leukemia Cells." Blood, vol. 101, no. 9, 2003, pp. 3648-57.
Wang S, Wang Z, Dent P, et al. Induction of tumor necrosis factor by bryostatin 1 is involved in synergistic interactions with paclitaxel in human myeloid leukemia cells. Blood. 2003;101(9):3648-57.
Wang, S., Wang, Z., Dent, P., & Grant, S. (2003). Induction of tumor necrosis factor by bryostatin 1 is involved in synergistic interactions with paclitaxel in human myeloid leukemia cells. Blood, 101(9), 3648-57.
Wang S, et al. Induction of Tumor Necrosis Factor By Bryostatin 1 Is Involved in Synergistic Interactions With Paclitaxel in Human Myeloid Leukemia Cells. Blood. 2003 May 1;101(9):3648-57. PubMed PMID: 12522001.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Induction of tumor necrosis factor by bryostatin 1 is involved in synergistic interactions with paclitaxel in human myeloid leukemia cells. AU - Wang,Shujie, AU - Wang,Zhiliang, AU - Dent,Paul, AU - Grant,Steven, Y1 - 2003/01/09/ PY - 2003/1/11/pubmed PY - 2003/6/21/medline PY - 2003/1/11/entrez SP - 3648 EP - 57 JF - Blood JO - Blood VL - 101 IS - 9 N2 - Interactions between the protein kinase C (PKC) activator/down-regulator bryostatin 1 and paclitaxel have been examined in human myeloid leukemia cells (U937) and in highly paclitaxel-resistant cells ectopically expressing a Bcl-2 phosphorylation loop-deleted protein (Delta Bcl-2). Treatment (24 hours) of wild-type cells with paclitaxel (eg, 5 to 20 nM) in combination with 10 nM bryostatin 1 induced a marked increase in mitochondrial damage (eg, cytochrome c and Smac/DIABLO [second mitochondria-derived activator of caspases/direct IAP binding protein with low pI] release), caspase activation, Bid cleavage, and apoptosis; moreover, bryostatin 1 circumvented the block to paclitaxel-induced mitochondrial injury and apoptosis conferred by ectopic expression of the loop-deleted protein. Coadministration of tumor necrosis factor (TNF) soluble receptors, or ectopic expression of CrmA or dominant-negative caspase-8, abrogated potentiation of paclitaxel-induced mitochondrial injury and apoptosis by bryostatin 1, implicating the extrinsic apoptotic pathway in this process. Similar events occurred in HL-60 leukemia cells. Potentiation of paclitaxel-induced apoptosis in wild-type and mutant cells by bryostatin 1 was associated with increases in TNF-alpha mRNA and protein and was mimicked by exogenous TNF-alpha. Coadministration of the selective PKC inhibitor GFX (1 microM) blocked the increase in TNF-alpha mRNA levels and apoptosis in bryostatin 1/paclitaxel-treated cells. Lastly, synchronization of cells in G(2)M increased their sensitivity to TNF-alpha-associated lethality. Collectively, these findings indicate that in U937 cells, bryostatin 1 promotes paclitaxel-mediated mitochondrial injury and apoptosis, and circumvents resistance to cell death conferred by loss of the Bcl-2 phosphorylation domain, through the PKC-dependent induction of TNF-alpha. They further suggest that this process is amplified by paclitaxel-mediated arrest of cells in G(2)M, where they are more susceptible to TNF-alpha-induced lethality. SN - 0006-4971 UR - https://www.unboundmedicine.com/medline/citation/12522001/Induction_of_tumor_necrosis_factor_by_bryostatin_1_is_involved_in_synergistic_interactions_with_paclitaxel_in_human_myeloid_leukemia_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/2002-09-2739 DB - PRIME DP - Unbound Medicine ER -