Jagiellonian University Medical College, Kraków, Poland.
J Cell Biochem. 2011 Aug;112(8):2115-24. doi: 10.1002/jcb.23132.
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®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.
激动素核昔（KR）是腺昔的 N6-取代衍生物。它是一种天然化合物，在椰子奶中以纳摩尔水平存在。KR 最初被证明选择性抑制癌细胞的增殖并诱导其凋亡。我们观察到 KR 不仅抑制了人类癌症，还抑制了正常细胞的生长（20-80%），并且这种作用强烈依赖于细胞的类型。在接触 KR 后，抗凋亡的 Bcl-2 蛋白下调，而促凋亡的 Bax 在正常和癌细胞系中上调。细胞用 KR 处理后，细胞质中的细胞色素 c 水平增加。细胞凋亡的活性（ApoFluor®Green 细胞凋亡活性测定法）以及 caspase-3（caspase-3 激活测定法）主要在癌细胞中增加。KR 处理细胞中核内和细胞质中前胱冬肽酶 9 及其活性形式的表达增加。相比之下，KR 对胱冬肽酶 8 的表达没有影响。结果表明，非恶性细胞对 KR 的敏感性低于其癌症类似物，并且 KR 很可能通过内在途径刺激癌细胞的凋亡机制。
