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β 2 ‐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
Exogenous β 2 ‐microglobulin (β 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. β 2 m treatment induced the release of cytochrome c and apoptosis‐inducing factor (AIF) from the mi...
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Published in: | International journal of cancer 2003-01, Vol.103 (3), p.316-327 |
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Main Authors: | , , , |
Format: | Article |
Language: | English |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Exogenous β
2
‐microglobulin (β
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. β
2
m treatment induced the release of cytochrome c and apoptosis‐inducing factor (AIF) from the mitochondria, but no change in mitochondrial membrane potential (ΔΨm) was observed during apoptosis, suggesting that cytochrome c may be released through a mechanism independent of mitochondrial permeability transition (MPT) pore formation. Moreover, the β
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 β
2
m‐induced apoptosis, while Western blot analysis revealed that caspases‐1, ‐2, ‐3, ‐6, ‐7, ‐8 and ‐9 are not activated during β
2
m‐induced apoptosis in these cells. These results collectively indicate that a post‐mitochondrial caspase‐dependent mechanism is involved in β
2
m‐induced apoptosis. Moreover, β
2
m significantly enhanced the production of reactive oxygen species (ROS) during 12–48 hr treatment, and β
2
m‐induced apoptosis was almost totally inhibited in cells pre‐treated with the antioxidant N‐acetylcysteine (NAC), providing evidence that β
2
m‐induced apoptosis in CCRF‐HSB‐2 cells is ROS‐dependent. Therefore, these results reveal that β
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. © 2002 Wiley‐Liss, Inc. |
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ISSN: | 0020-7136 1097-0215 |
DOI: | 10.1002/ijc.10828 |