Cucurbitacin B induces inhibitory effects via CIP2A/PP2A/Akt pathway in glioblastoma multiforme.
Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a human oncoprotein that is overexpressed in multiple types of tumors and promotes the proliferation and transformation of cancer cells. However, whether CIP2A can be a new drug target for human glioblastoma multiforme (GBM) is largely unclear. In the present study, we demonstrated that the overexpression of CIP2A promotes invasive behavior in GBM, and a natural compound, cucurbitacin B (CuB), shows an anti-proliferative and anti-invasion effect in GBM cell lines. CuB effectively induces apoptosis, downregulates CIP2A expression and its downstream signaling molecule, phospho-Akt, and upregulates protein phosphatase 2A (PP2A) activity. Overexpression of CIP2A reduced CuB-inhibited growth and invasion in GBM cells. Silencing CIP2A enhanced CuB-induced invasion inhibition and apoptosis in GBM. CuB combined with cisplatin synergistically inhibited GBM cells. CuB also inhibited tumor growth in murine models. Western blot results further revealed that CuB downregulates CIP2A, and phospho-Akt in vivo. In summary, inhibition of CIP2A determines the effects of CuB-induced invasive behavior inhibition and apoptosis in GBM cells. These characteristics render CuB as a promising candidate drug for further development and for designing new effective CIP2A inhibitors.
['Qin|Shanshan|S|', 'Li|Jing|J|', 'Si|Yuan|Y|', 'He|Zhongwei|Z|', 'Zhang|Te|T|', 'Wang|Dawei|D|', 'Liu|Xuewen|X|', 'Guo|Yang|Y|', 'Zhang|Liang|L|', 'Li|Shan|S|', 'Li|Qiang|Q|', 'Liu|Ying|Y|0000-0001-7423-5169']
D000818:Animals D017209:Apoptosis D045744:Cell Line, Tumor D049109:Cell Proliferation D002945:Cisplatin D015536:Down-Regulation D005260:Female D015972:Gene Expression Regulation, Neoplastic D005909:Glioblastoma D006801:Humans D008297:Male D051379:Mice D008819:Mice, Nude D009361:Neoplasm Invasiveness D054648:Protein Phosphatase 2 D051057:Proto-Oncogene Proteins c-akt D015398:Signal Transduction D014315:Triterpenes D015854:Up-Regulation
cucurbitacin B CIP2A glioblastoma invasive behavior apoptosis