Therapeutic potential of HIV protease-activable CASP3

Development of a therapeutic application of CASP3/caspase 3/CPP32, an executor of apoptosis, has been challenging because regulation of its activation is complicated. This study aimed to inhibit cancer cell growth and human immunodeficiency virus type 1 (HIV-1) propagation through a CASP3 mutant, CA...

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Bibliographic Details
Published in:Scientific reports 2012-04, Vol.2 (1), p.359-359, Article 359
Main Authors: Miyauchi, Kosuke, Urano, Emiko, Takizawa, Mari, Ichikawa, Reiko, Komano, Jun
Format: Article
Language:English
Subjects:
631/208/2489/201
631/326/596
631/61/338
631/67/581
Apoptosis
Base Sequence
Cancer
Caspase
Caspase 3 - metabolism
Caspase 3 - therapeutic use
Caspase-3
Cell Line
Cytoplasm
Data processing
DNA Primers
Gag protein
HIV
HIV Infections - drug therapy
HIV Protease - metabolism
Human immunodeficiency virus
Humanities and Social Sciences
Humans
Leukemia
Lymphoma - drug therapy
multidisciplinary
Nanoparticles
Polymerase Chain Reaction
Proteinase
Science
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Summary:Development of a therapeutic application of CASP3/caspase 3/CPP32, an executor of apoptosis, has been challenging because regulation of its activation is complicated. This study aimed to inhibit cancer cell growth and human immunodeficiency virus type 1 (HIV-1) propagation through a CASP3 mutant, CASP3*, activable by HIV-1-encoded aspartate protease. Active CASP3* was delivered to leukemic cells using a protein transduction vehicle, the lentivirus-like nanoparticle (LENA), which should contain thousands of CASP3*-Gag protein molecules and release the activated CASP3* into the target cell cytoplasm. CASP3*-LENA induced apoptosis in various types of leukemic cells. In addition to being effective against leukemic cells, constitutive expression of CASP3* restricted HIV-1 propagation in SUP-T1 cells. The attenuation of HIV-1 replication in SUP-T1/CASP3* cells was attributed to the elimination of HIV-1-infected cells by apoptosis. These data suggest that CASP3* has therapeutic potential against both lymphoid malignancies and HIV-1 infection.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep00359