stellettin-b and Leukemia--Myelogenous--Chronic--BCR-ABL-Positive

stellettin-b has been researched along with Leukemia--Myelogenous--Chronic--BCR-ABL-Positive* in 1 studies

Other Studies

1 other study(ies) available for stellettin-b and Leukemia--Myelogenous--Chronic--BCR-ABL-Positive

Article	Year
Stellettin B induces apoptosis in human chronic myeloid leukemia cells via targeting PI3K and Stat5. Oncotarget, 2017, Apr-25, Volume: 8, Issue:17 Novel agents are still urgently expected for therapy of chronic myeloid leukemia (CML). The in vitro anti-leukemia activity of Stellettin B (Stel B), a triterpenoid we isolated from marine sponge Jaspis stellifera, on human CML K562 and KU812 cells was recently investigated. Stel B inhibited K562 and KU812 cell proliferation with IC50 as 0.035 μM and 0.95 μM respectively. While no obvious cell cycle arrest was observed, apoptosis was induced in K562 cells after Stel B treatment. The Stel B-induced apoptosis might be in mitochondrial pathway, with increase of Bad and Bax, decrease of Bcl-2 and activation of caspase-9. In addition, dose-dependent increase of reactive oxygen species (ROS) and loss of mitochondrial membrane potential (MMP) occurred. Meanwhile, Stel B inhibited phosphorylation of Stat5, expression of 4 PI3K catalytic isoforms, and phosphorylation of the downstream effectors including PDK1 and Akt, suggesting that inhibition against Stat5 and PI3K might be involved in the apoptosis-inducing effect. Combination of Stel B with Imatinib with ratio as IC50 Stel B : 5×IC50 Imatinib led to synergistic effect. Stel B might become a promising candidate for CML therapy alone or together with Imatinib. Topics: Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; bcl-2-Associated X Protein; bcl-Associated Death Protein; Caspase 9; Cell Cycle Checkpoints; Cell Proliferation; Drug Resistance, Neoplasm; Drug Synergism; Flow Cytometry; Humans; Imatinib Mesylate; Inhibitory Concentration 50; K562 Cells; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Membrane Potential, Mitochondrial; Mitochondria; Phosphatidylinositol 3-Kinases; Phosphorylation; Porifera; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-bcl-2; Pyruvate Dehydrogenase Acetyl-Transferring Kinase; Reactive Oxygen Species; RNA Interference; RNA, Small Interfering; Signal Transduction; STAT5 Transcription Factor; Triterpenes; Tumor Suppressor Proteins	2017

Article

Year

Stellettin B induces apoptosis in human chronic myeloid leukemia cells via targeting PI3K and Stat5.

Oncotarget, 2017, Apr-25, Volume: 8, Issue:17

Novel agents are still urgently expected for therapy of chronic myeloid leukemia (CML). The in vitro anti-leukemia activity of Stellettin B (Stel B), a triterpenoid we isolated from marine sponge Jaspis stellifera, on human CML K562 and KU812 cells was recently investigated. Stel B inhibited K562 and KU812 cell proliferation with IC50 as 0.035 μM and 0.95 μM respectively. While no obvious cell cycle arrest was observed, apoptosis was induced in K562 cells after Stel B treatment. The Stel B-induced apoptosis might be in mitochondrial pathway, with increase of Bad and Bax, decrease of Bcl-2 and activation of caspase-9. In addition, dose-dependent increase of reactive oxygen species (ROS) and loss of mitochondrial membrane potential (MMP) occurred. Meanwhile, Stel B inhibited phosphorylation of Stat5, expression of 4 PI3K catalytic isoforms, and phosphorylation of the downstream effectors including PDK1 and Akt, suggesting that inhibition against Stat5 and PI3K might be involved in the apoptosis-inducing effect. Combination of Stel B with Imatinib with ratio as IC50 Stel B : 5×IC50 Imatinib led to synergistic effect. Stel B might become a promising candidate for CML therapy alone or together with Imatinib.

Topics: Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; bcl-2-Associated X Protein; bcl-Associated Death Protein; Caspase 9; Cell Cycle Checkpoints; Cell Proliferation; Drug Resistance, Neoplasm; Drug Synergism; Flow Cytometry; Humans; Imatinib Mesylate; Inhibitory Concentration 50; K562 Cells; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Membrane Potential, Mitochondrial; Mitochondria; Phosphatidylinositol 3-Kinases; Phosphorylation; Porifera; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-bcl-2; Pyruvate Dehydrogenase Acetyl-Transferring Kinase; Reactive Oxygen Species; RNA Interference; RNA, Small Interfering; Signal Transduction; STAT5 Transcription Factor; Triterpenes; Tumor Suppressor Proteins

2017