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標題: Brain tumor senescence might be mediated by downregulation of S-phase kinase-associated protein 2 via butylidenephthalide leading to decreased cell viability
作者: Huang, Mao-Hsuan
Lin, Shinn-Zong
Lin, Po-Cheng
Chiou, Tzyy-Wen
Harn, Yeu-Wei
Ho, Li-Ing
Chan, Tzu-Min
Chou, Chih-Wei
Chuang, Chang-Han
Su, Hong-Lin
Harn, Horng-Jyh
關鍵字: Animals;Brain Neoplasms;Cell Aging;Cell Line, Tumor;Cell Proliferation;Cell Survival;Down-Regulation;Glioblastoma;Humans;Mice;Mice, Nude;Phthalic Anhydrides;S-Phase Kinase-Associated Proteins;Sp1 Transcription Factor
Project: Tumor Biology, Volume 35, Issue 5, Page(s) 4875-4884.
Developing an effective drug for treating human glioblastoma multiform (GBM) has been investigated persistently. A pure compound butylidenephthalide (BP), isolated from Angelica sinensis, has been shown the activities to arrest the growth and initiate apoptosis of GBM in our previous reports. In this study, we further demonstrated that BP treatment accelerates the cell senescence in a dose-dependent manner in vitro and in vivo. S-phase kinase-associated protein 2 (Skp2), a proto-oncogene, is generally upregulated in cancer. We found that it was downregulated in BP-treated GBM cells. The downregulation of Skp2 is parallel with increasing p16 and p21 expression which causes G0/G1 arrest and tumor cell senescence. We also found that restoring the Skp2 protein level by exogenous overexpression prevents the BP-induced cell senescence. Therefore, the linkage between cell senescence and Skp2 expression is strengthened. Promoter binding analysis further detailed that the BP-mediated SP1 reduction might involve in the Skp2 downregulation. In summary, these results emphasize that BP-triggered senescence in GBM cells is highly associated with its control on Skp2 regulation.
ISSN: 1010-4283
DOI: 10.1007/s13277-014-1639-0
Appears in Collections:生命科學系所

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