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Beta2-microglobulin Induces Caspase-Dependent Apoptosis in the CCRF-HSB-2 Human Leukemia Cell Line Independently of the caspase-3, -8 and -9 Pathways but Through Increased Reactive Oxygen Species

Beta2-microglobulin Induces Caspase-Dependent Apoptosis in the CCRF-HSB-2 Human Leukemia Cell Line Independently of the caspase-3, -8 and -9 Pathways but Through Increased Reactive Oxygen Species

John Gordon, Ching-Huang Wu, Mojgan Rastegar, Ahmad R Safa

Int J Cancer. 2003 Jan 20;103(3):316-27.

PMID: 12471614

Abstract:

Exogenous beta(2)-microglobulin (beta(2)m) induces significant apoptosis in the CCRF-HSB-2 human lymphoblastic leukemia cell line as detected by DNA fragmentation, DAPI staining and annexin V binding assay. beta(2)m treatment induced the release of cytochrome c and apoptosis-inducing factor (AIF) from the mitochondria, but no change in mitochondrial membrane potential (DeltaPsim) was observed during apoptosis, suggesting that cytochrome c may be released through a mechanism independent of mitochondrial permeability transition (MPT) pore formation. Moreover, the beta(2)m-induced release of cytochrome c and AIF from the mitochondria in CCRF-HSB-2 cells was caspase-independent, since Z-VAD-fmk, a general inhibitor of caspases, did not block the release of these factors. However, Z-VAD-fmk treatment significantly blocked beta(2)m-induced apoptosis, while Western blot analysis revealed that caspases-1, -2, -3, -6, -7, -8 and -9 are not activated during beta(2)m-induced apoptosis in these cells. These results collectively indicate that a post-mitochondrial caspase-dependent mechanism is involved in beta(2)m-induced apoptosis. Moreover, beta(2)m significantly enhanced the production of reactive oxygen species (ROS) during 12-48 hr treatment, and beta(2)m-induced apoptosis was almost totally inhibited in cells pre-treated with the antioxidant N-acetylcysteine (NAC), providing evidence that beta(2)m-induced apoptosis in CCRF-HSB-2 cells is ROS-dependent. Therefore, these results reveal that beta(2)m-induced apoptosis in CCRF-HSB-2 cells may occur through an unknown caspase-dependent and ROS-dependent mechanism(s) that is associated with cytochrome c and AIF release from mitochondria, but is independent of the caspase -3, -8 and -9 pathways.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR424977	Caspase 2 human			Price

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