Withaferin A arrested glioblastoma cells at G_2/M phase and induced apoptosis through intrinsic pathway |
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| Institution: | ;1.The State Key Laboratory of Bioactive Substance and Function of Natural Medicines;2.Key Laboratory of Drug Target Research and Drug Screen;3.Institute of Materia Medica;4.Chinese Academy of Medical Science and Peking Union Medical College |
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| Abstract: | OBJECTIVE To explore the efficacy and mechanism of withaferin A(WA) in Glioblastoma multiforme(GBM, WHO grade Ⅳ astrocytoma). METHODS Cell viability assay and nude mice xenograft model were used to evaluate the efficacy of WA in GBM. Flow cytometry was performed to detection the effects of WA on apoptosis and cell cycle of GBM. Western blotting and si RNA transfection were carried out to check signaling pathway induced by WA. RESULTS WA significantly inhibited the growth of GBM in vivo and in vitro. WA treatment triggered the intrinsic apoptosis of GBM cells by upregulating expression of Bim and Bad, and arrested GBM cells at G_2/M phase through dephosphorylating Thr161 of CDK1 by activating p53-independent p21 up-regulation. In addition, p21 knockdown restored progress of cell cycle and cell viability by down-regulating the expression of Bad rather than Bim. CONCLUSION WA arrested GBM cells at G_2/M phase and triggered the intrinsic apoptosis through p21-Bad axis. |
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