title: Bone morphogenetic protein 4 inhibits cell proliferation and induces apoptosis in glioma stem cells.
abstract: Glioma stem cells (GSCs), which are originated from transformed neural stem cells, are tumor-initiating cells of glioma, the most common primary malignant neoplasm of the central nervous system. Extensive studies have shown that bone morphogenetic protein 4 (BMP4) plays an important role in the differentiation and proliferation of neural stem cells. To seek the functions and mechanisms of BMP4 in GSCs, GSCs isolated from U87 human glioma cells by using vincristine were exposed to BMP4 protein. This study shows that BMP4 inhibited U87 GSC proliferation (p < 0.01) via downregulation of cyclin D1 level and promoted GSC apoptosis through induction of Bax expression and inhibition of Bcl-2 and Bcl-xL levels. Thus, these results indicate a new approach of GSC-based glioma treatment.
authors.affiliation: Department of Neurosurgery, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, People's Republic of China.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Zhou
authors.forename: Lihua
authors.initials: L
authors.lastname: Sun
authors.forename: Yingyi
authors.initials: Y
authors.lastname: Wang
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Wu
authors.forename: Jiong
authors.initials: J
authors.lastname: Geng
authors.forename: Weifeng
authors.initials: W
authors.lastname: Miu
authors.forename: Yi
authors.initials: Y
authors.lastname: Pu
authors.forename: Yongping
authors.initials: Y
authors.lastname: You
authors.forename: Zhengxiang
authors.initials: Z
authors.lastname: Yang
authors.forename: Ning
authors.initials: N
authors.lastname: Liu
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D055415:Bone Morphogenetic Protein 4 / Q000494:pharmacology* / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D048708:Cell Growth Processes / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D019938:Cyclin D1 / Q000096:biosynthesis / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D014750:Vincristine / Q000494:pharmacology; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis / Q000235:genetics; D051020:bcl-X Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: C494811:BCL2L1 protein, human; D055415:Bone Morphogenetic Protein 4; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D019938:Cyclin D1; D014750:Vincristine