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    Khat (Catha edulis)-induced apoptosis is inhibited by antagonists of caspase-1 and -8 in human leukaemia cells.

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    Date
    2004-11
    Author
    Dimba, EA
    Gjertsen, BT
    Bredholt, T
    Fossan, KO
    Costea, DE
    Francis, GW
    Johannessen, AC
    Vintermyr, OK
    Type
    Article
    Language
    en
    Metadata
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    Abstract
    Khat chewing is a widespread habit that has a deep-rooted sociocultural tradition in Africa and the Middle East. The biological effects of khat are inadequately investigated and controversial. For the first time, we show that an organic extract of khat induces a selective type of cell death having all morphological and biochemical features of apoptotic cell death. Khat extract was shown to contain the major alkaloid compounds cathinone and cathine. The compounds alone and in combination also induced apoptosis. Khat-induced apoptosis occurred synchronously in various human cell lines (HL-60, NB4, Jurkat) within 8 h of exposure. It was partially reversed after removal of khat and the effect was dependent on de novo protein synthesis, as demonstrated by cotreatment with cycloheximide. The cell death was blocked by the pan-caspase inhibitor Z-VAD-fmk, and also by submicromolar concentrations of Z-YVAD-fmk and Z-IETD-fmk, inhibitors of caspase-1 and -8, respectively. The 50% inhibition constant (IC(50)) for khat (200 microg ml(-1))-induced apoptosis by Z-VAD-fmk, Z-YVAD-fmk and Z-IETD-fmk was 8 x 10(-7) M as compared to 2 x 10(-8) M and 8 x 10(-8) M, respectively. Western blot analysis showed a specific cleavage of procaspase-3 in apoptotic cells, which was inhibited by Z-VAD-fmk. The cell death by khat was more sensitively induced in leukaemia cell lines than in human peripheral blood leukocytes. It is concluded that khat induces a rather swift and sensitive cell death by apoptosis through mechanisms involving activation of caspase-1, -3 and -8.
    URI
    http://hinari-gw.who.int/whalecomwww.ncbi.nlm.nih.gov/whalecom0/pubmed/15477863
    http://erepository.uonbi.ac.ke:8080/xmlui/handle/123456789/55220
    Citation
    Br J Cancer. 2004 Nov 1;91(9):1726-34.
    Publisher
    University of Nairobi,
     
    Department of Oral and Maxillofacial Radiology
     
    Subject
    Khat
    leukaemia cells
    apoptosis
    caspases
    cathinone
    cathine
    Collections
    • Faculty of Health Sciences (FHS) [10415]

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