Hueng Dueng-Yuan, Hsieh Ching-Hsuan, Cheng Yu-Chen, Tsai Wen-Chiuan, Chen Ying
Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Penghu Branch of Tri-Service General Hospital, Magong, Penghu, Taiwan; Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan.
Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan.
J Nutr Biochem. 2017 Mar;41:109-116. doi: 10.1016/j.jnutbio.2016.12.008. Epub 2016 Dec 29.
Cordycepin, a nucleoside-derivative-isolated form Cordyceps militaris, has been reported to suppress tumor cell proliferation and cause apoptosis. This study investigates the effect of cordycepin on the migration of human glioblastoma cells. Cordycepin suppressed the migration of the human glioblastoma cell lines U87MG and LN229 in transwell and wound healing assays. Cordycepin decreased protein expression of integrin α1, focal adhesion kinase (FAK), p-FAK, paxillin and p-paxillin. The lysosomal inhibitor NHCl blocked the ability of cordycepin to inhibit focal adhesion protein expression and glioma cell migration. In addition, the protein phosphatase inhibitors calyculin A and okadaic acid blocked the cordycepin-mediated reduction in p-Akt, p-FAK and migration. Hematoxylin and eosin staining of mouse xenografts demonstrated that cordycepin reduced brain tumor size in vivo. In conclusion, cordycepin inhibited migration of human glioblastoma cells by affecting lysosomal degradation and protein phosphatase activation. This pathway may be a useful target for clinical therapy in the future.
虫草素是一种从蛹虫草中分离得到的核苷衍生物,据报道它能抑制肿瘤细胞增殖并诱导细胞凋亡。本研究旨在探讨虫草素对人胶质母细胞瘤细胞迁移的影响。在Transwell实验和伤口愈合实验中,虫草素抑制了人胶质母细胞瘤细胞系U87MG和LN229的迁移。虫草素降低了整合素α1、粘着斑激酶(FAK)、磷酸化FAK、桩蛋白和磷酸化桩蛋白的蛋白表达。溶酶体抑制剂NHCl阻断了虫草素抑制粘着斑蛋白表达和胶质瘤细胞迁移的能力。此外,蛋白磷酸酶抑制剂花萼海绵诱癌素A和冈田酸阻断了虫草素介导的p-Akt、p-FAK降低以及迁移抑制。对小鼠异种移植瘤进行苏木精-伊红染色显示,虫草素在体内减小了脑肿瘤的大小。总之,虫草素通过影响溶酶体降解和蛋白磷酸酶激活来抑制人胶质母细胞瘤细胞的迁移。这一途径可能是未来临床治疗的一个有用靶点。