Khat (Catha edulis)-induced apoptosis is inhibited by antagonists of caspase-1 and -8 in human leukaemia cells.
Khat (Catha edulis)-induced apoptosis is inhibited by antagonists of caspase-1 and -8 in human leukaemia cells.
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DOI：
10.1038/sj.bjc.6602197
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发表时间：
2004-11-01
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
咀嚼阿拉伯茶是非洲和中东一种普遍的习惯，具有根深蒂固的社会文化传统。阿拉伯茶的生物效应没有得到充分的调查，而且存在争议。对于第一次，我们表明，阿拉伯茶的有机提取物诱导的选择性类型的细胞死亡具有所有的形态和生物化学特征的细胞凋亡。阿拉伯茶提取物中含有主要的生物碱化合物卡西酮和卡西碱。化合物单独和组合也诱导细胞凋亡。Khat诱导的细胞凋亡发生在各种人类细胞系（HL-60，NB4，Jurkat）在8小时内曝光同步。这是部分逆转后，去除阿拉伯茶和效果是依赖于从头蛋白质合成，证明了与放线菌酮共处理。细胞死亡被泛半胱天冬酶抑制剂Z-VAD-favorite阻断，并且还被亚微摩尔浓度的Z-YVAD-favorite和Z-IETD-favorite（分别为半胱天冬酶-1和-8的抑制剂）阻断。对于阿茶（200 μ g ml − 1）诱导的细胞凋亡，Z-VAD-falcohol、Z-YVAD-falcohol和Z-IETD-falcohol的50%抑制常数（IC 50）为8 × 10 − 7 M，相比之下，分别为2 × 10 − 8 M和8 × 10 − 8 M。Western blot分析表明，在凋亡细胞中，caspase-3的特异性切割，这是由Z-VAD-fetamine抑制。在白血病细胞系中，阿茶引起的细胞死亡比在人外周血白细胞中更敏感。它的结论是，阿拉伯茶诱导一个相当迅速和敏感的细胞死亡的凋亡通过机制，涉及激活半胱天冬酶-1，3和-8。
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 (IC50) for khat (200 μg ml−1)-induced apoptosis by Z-VAD-fmk, Z-YVAD-fmk and Z-IETD-fmk was 8 × 10−7 M as compared to 2 × 10−8 M and 8 × 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.
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影响因子：
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作者：
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