Cordycepin (3′-deoxyadenosine) inhibits the growth of B16-BL6 mouse melanoma cells through the stimulation of adenosine A3 receptor followed by glycogen synthase kinase-3β activation and cyclin D1 suppression
Cordycepin (3′-deoxyadenosine) inhibits the growth of B16-BL6 mouse melanoma cells through the stimulation of adenosine A3 receptor followed by glycogen synthase kinase-3β activation and cyclin D1 suppression
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DOI：
10.1007/s00210-007-0218-y
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发表时间：
2008-06-01
影响因子：
3.6
通讯作者：
Nakamura, Kazuki
中科院分区：
文献类型：
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作者：
Yoshikawa, Noriko;Yamada, Shizuo;Nakamura, Kazuki
冬虫夏草是一种寄生在鳞翅目幼虫上的真菌，已被用作传统中药。我们之前报道了B16-BL6小鼠黑色素瘤（B16-BL6）细胞的生长受到冬虫夏草活性成分虫草素（3'-脱氧腺苷）的抑制，而其作用被选择性腺苷A（3）受体拮抗剂MRS1191拮抗。在本研究中，使用 [I-125]-AB-MECA（一种选择性腺苷 A(3) 受体激动剂）进行的放射性配体结合测定表明，B16-BL6 细胞表达腺苷 A(3) 受体，并且虫草素与这些受体结合。我们还使用特异性腺苷 A(3) 受体拮抗剂 MRS1523 和 MRS1220 证实了腺苷 A(3) 受体参与虫草素的作用。接下来，靛玉红（一种糖原合成酶激酶 3 β (GSK-3 β) 抑制剂）可以拮抗虫草素引起的生长抑制。此外，使用蛋白质印迹分析发现，虫草素可降低 B16-BL6 细胞中细胞周期蛋白 D-1 的水平。总之，本研究证明虫草素通过刺激腺苷 A(3) 受体以及随后的 Wnt 信号通路（包括 GSK-3 beta 激活和细胞周期蛋白 D-1 抑制）来抑制 B16-BL6 细胞的增殖。
Cordyceps sinensis, a parasitic fungus on the larvae of Lepidoptera, has been used as a traditional Chinese medicine. We previously reported that the growth of B16-BL6 mouse melanoma (B16-BL6) cells was inhibited by cordycepin (3'-deoxyadenosine), an active ingredient of C. sinensis, and its effect was antagonized by MRS1191, a selective adenosine A(3) receptor antagonist. In this study, the radioligand binding assay using [I-125]-AB-MECA (a selective adenosine A(3) receptor agonist) has shown that B16-BL6 cells express adenosine A(3) receptors and that cordycepin binds to these receptors. We also confirmed the involvement of adenosine A(3) receptors in the action of cordycepin using MRS1523 and MRS1220, specific adenosine A(3) receptor antagonists. Next, indirubin, a glycogen synthase kinase-3 beta (GSK-3 beta) inhibitor, antagonized the growth suppression induced by cordycepin. Furthermore, the level of cyclin D-1 protein in B16-BL6 cells was decreased by cordycepin using Western blot analysis. In conclusion, this study demonstrated that cordycepin inhibits the proliferation of B16-BL6 cells by stimulating adenosine A(3) receptors followed by the Wnt signaling pathway, including GSK-3 beta activation and cyclin D-1 inhibition.