Effects of Kinetin Riboside on Proliferation and Proapoptotic Activities in Human Normal and Cancer Cell Lines
Effects of Kinetin Riboside on Proliferation and Proapoptotic Activities in Human Normal and Cancer Cell Lines
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DOI：
10.1002/jcb.23132
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发表时间：
2011-08-01
影响因子：
4
通讯作者：
Laidler, Piotr
中科院分区：
文献类型：
--
作者：
Dudzik, Paulina;Dulinska-Litewka, Joanna;Laidler, Piotr
激动素核苷(KR)是腺苷的N6取代衍生物。它是一种天然化合物，存在于椰奶中，分子水平为纳米级。KR最初被证明可以选择性地抑制癌细胞的增殖并诱导其凋亡。我们观察到KR不仅抑制了人类癌细胞的生长(20%-80%)，而且这种抑制作用强烈地依赖于细胞的类型。当KR暴露时，抗凋亡的Bcl2蛋白下调，而促凋亡的Bax在正常和癌细胞系中上调。KR处理细胞后，胞浆中细胞色素c水平升高。Caspase活性(ApoFluor(R)Green Caspase活性分析)和caspase-3(Caspase-3激活分析)活性主要在癌细胞中增加。KR处理组细胞核和胞浆中原天冬氨酸氨基转移酶9及其活性形式的表达均升高。相反，KR对caspase-8的表达没有影响。结果表明，非肿瘤细胞对KR的敏感性低于其肿瘤类似物，KR很可能通过内源性途径刺激肿瘤细胞的凋亡机制。J.细胞。生物化学。112：2115-2124,2011。(C)2011年Wiley-Liss，Inc.
Kinetin riboside (KR) is a N6-substituted derivative of adenosine. It is a natural compound which occurs in the milk of coconuts on the nanomole level. KR was initially shown to selectively inhibit proliferation of cancer cells and induce their apoptosis. We observed that KR inhibited growth (20-80%) of not only human cancer, but also normal cells and that this effect strongly depended on the type of cells. The anti-apoptotic Bcl-2 protein was downregulated, while proapoptotic Bax was upregulated in normal as well as in cancer cell lines, upon exposure to KR. Cytochrome c level increased in the cytosol upon treatment of cells with KR. The activity of caspases (ApoFluor (R) Green Caspase Activity Assay), as well as caspase-3 (caspase-3 activation assay) were increased mainly in cancer cells. The expression of procaspase 9 and its active form in the nucleus as well as in cytosol of KR-treated cells was elevated. In contrast, no effect of KR on caspase 8 expression was noted. The results indicated that non-malignant cells were less sensitive to KR then their cancer analogs and that KR most likely stimulated apoptosis mechanism of cancer cells through the intrinsic pathway. J. Cell. Biochem. 112: 2115-2124, 2011. (C) 2011 Wiley-Liss, Inc.