Cryptotanshinone inhibits cancer cell proliferation by suppressing Mammalian target of rapamycin-mediated cyclin D1 expression and Rb phosphorylation.
Cryptotanshinone inhibits cancer cell proliferation by suppressing Mammalian target of rapamycin-mediated cyclin D1 expression and Rb phosphorylation.
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DOI：
10.1158/1940-6207.capr-10-0020
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发表时间：
2010-08
期刊：
影响因子：
--
通讯作者：
Huang S
中科院分区：
文献类型：
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作者：
Chen W;Luo Y;Liu L;Zhou H;Xu B;Han X;Shen T;Liu Z;Lu Y;Huang S
隐丹参酮(CPT)是从丹参中分离得到的一种天然化合物，是一种潜在的抗癌药物。然而，人们对其抗癌机制知之甚少。在这里，我们表明，CPT通过将细胞阻滞在细胞周期的G1/G0期来抑制癌细胞的增殖。这与抑制细胞周期蛋白D1的表达和视网膜母细胞瘤(Rb)蛋白的磷酸化有关。此外，我们发现CPT抑制了哺乳动物雷帕霉素靶标(MTOR)的信号通路，mTOR是细胞增殖的中央调节因子。CPT以浓度和时间依赖的方式抑制I型胰岛素样生长因子(IGF-1)或10%胎牛血清(FBS)刺激的mTOR、p70 S6激酶1(S6K1)和真核细胞起始因子4E(EIF4E)结合蛋白1(4E-BP1)的磷酸化，证明了这一点。MTOR的表达可以抵抗CPT对细胞周期蛋白D1表达和Rb磷酸化的抑制，以及对细胞生长的抑制。结果表明，CPT是一种新型的抗增殖剂。
Cryptotanshinone (CPT), a natural compound isolated from the plant Salvia miltiorrhiza Bunge, is a potential anticancer agent. However, little is known about its anticancer mechanism. Here we show that CPT inhibited cancer cell proliferation by arresting cells in G1/G0 phase of the cell cycle. This is associated with inhibiting expression of cyclin D1 and phosphorylation of retinoblastoma (Rb) protein. Furthermore, we found that CPT inhibited the signaling pathway of the mammalian target of rapamycin (mTOR), a central regulator of cell proliferation. This is evidenced by the findings that CPT inhibited type I insulin-like growth factor (IGF-1) or 10% fetal bovine serum (FBS)-stimulated phosphorylation of mTOR, p70 S6 kinase 1 (S6K1) and eukaryotic initiation factor 4E (eIF4E) binding protein 1 (4E-BP1), in a concentration- and time-dependent manner. Expression of constitutively active mTOR conferred resistance to CPT inhibition of cyclin D1 expression and Rb phosphorylation, as well as cell growth. The results suggest that CPT is a novel anti-proliferative agent.