Neferine, an alkaloid ingredient in lotus seed embryo, inhibits proliferation of human osteosarcoma cells by promoting p38 MAPK-mediated p21 stabilization
Neferine, an alkaloid ingredient in lotus seed embryo, inhibits proliferation of human osteosarcoma cells by promoting p38 MAPK-mediated p21 stabilization
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莲心碱是莲子胚中的一种生物碱成分，通过促进 p38 MAPK 介导的 p21 稳定来抑制人骨肉瘤细胞的增殖
DOI：
10.1016/j.ejphar.2011.12.035
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发表时间：
2012-02-29
影响因子：
5
通讯作者：
Shao, Changshun
中科院分区：
文献类型：
--
作者：
Zhang, Xiyu;Liu, Zhaojian;Shao, Changshun
鉴定具有抗肿瘤活性的天然产物对于癌症的化学预防和治疗是非常宝贵的。莲子的胚被认为具有保健作用，在世界上的一些地方被用作饮料。本文研究莲胚中主要生物碱成分甲基莲心碱对人骨肉瘤细胞的作用及其机制。我们发现甲基莲心碱对人骨肉瘤细胞具有有效的生长抑制作用，但对非肿瘤性人成骨细胞没有作用。甲基莲心碱对人骨肉瘤细胞的抑制作用主要归因于细胞周期阻滞在G1期。G1期阻滞的诱导是p21（WAF 1/CIP 1）依赖性的，但不依赖于p53或RB（视网膜母细胞瘤相关蛋白）。甲基莲心碱对p21的上调是由于p21蛋白半衰期的增加。我们研究了已知影响p21稳定性的四种激酶，发现p38 MAPK和JNK被甲基莲心碱激活。然而，只有SB 203580（p38的抑制剂），而不是SP 600125（JNK的抑制剂），可以减弱p21响应甲基莲心碱的上调。此外，甲基莲心碱的p21稳定作用被废除时，p38被沉默的RNA干扰。最后，我们发现甲基莲心碱处理导致依赖于p38的p21在Ser 130的磷酸化增加。我们的研究结果首次显示甲基莲心碱的直接抗肿瘤作用，表明甲基莲心碱的消费可能具有癌症预防和癌症治疗的益处。(C)2011 Elsevier B. V.保留所有权利。
Identification of natural products that have antitumor activity is invaluable to the chemoprevention and therapy of cancer. The embryos of lotus (Nelumbo nucifera) seeds are consumed in beverage in some parts of the world for their presumed health-benefiting effects. In this report we studied the effects of neferine, a major alkaloid component in lotus embryos, on human osteosarcoma cells and the underlying mechanisms. We found that neferine possessed a potent growth-inhibitory effect on human osteosarcoma cells, but not on non-neoplastic human osteoblast cells. The inhibitory effect of neferine on human osteosarcoma cells was largely attributed to cell cycle arrest at G1. The induction of G1 arrest was p21(WAF1/CIP1)-dependent, but was independent of p53 or RB (retinoblastoma-associated protein). The up-regulation of p21 by neferine was due to an increase in the half-life of p21 protein. We examined four kinases that are known to affect the stabilization of p21, and found that p38 MAPK and JNK were activated by neferine. However, only SB203580 (an inhibitor of p38), but not SP600125 (the inhibitor of JNK), can attenuate the up-regulation of p21 in response to neferine. Furthermore, the p21-stabilizing effect of neferine was abolished when p38 was silenced by RNA interference. Finally, we showed that neferine treatment led to an increased phosphorylation of p21 at Ser130 that was dependent on p38. Our results for the first time showed a direct antitumor effect of neferine, suggesting that consumption of neferine may have cancer-preventive and cancer-therapeutic benefit. (C) 2011 Elsevier B.V. All rights reserved.