Triptolide inhibits proliferation and invasion of malignant glioma cells

• Published in: Journal of neuro-oncology 2012-08, Vol.109 (1), p.53-62
• Main Authors: Zhang, Haipeng, Zhu, Wenbo, Su, Xingwen, Wu, Sihan, Lin, Yuan, Li, Jingjie, Wang, Youqiong, Chen, Jingkao, Zhou, Yuxi, Qiu, Pengxin, Yan, Guangmei, Zhao, Shujin, Hu, Jun, Zhang, Jingxia
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents, Alkylating - pharmacology; Apoptosis - drug effects; Blood-brain barrier; Blotting, Western; Brain Neoplasms - drug therapy; Brain Neoplasms - metabolism; Brain Neoplasms - pathology; Brain tumors; cdc42 GTP-Binding Protein - metabolism; Cdc42 protein; Cell cycle; Cell Cycle - drug effects; Cell migration; Cell Movement - drug effects; Cell proliferation; Cell Proliferation - drug effects; Chemotherapy; Cyclin-Dependent Kinases - metabolism; Diterpenes - pharmacology; Drug resistance; Epoxy Compounds - pharmacology; Female; Flow Cytometry; G1 phase; Glioma; Glioma - drug therapy; Glioma - metabolism; Glioma - pathology; Glioma cells; Guanosinetriphosphatase; Laboratory Investigation; Lipids; Medicine; Medicine & Public Health; Mice; Mice, Nude; Neoplasm Invasiveness; Neurology; Oncology; Phenanthrenes - pharmacology; Phosphorylation; rac GTP-Binding Proteins - metabolism; rac1 GTP-Binding Protein - metabolism; Rac1 protein; RAC2 GTP-Binding Protein; Radiotherapy; Rats; Retinoblastoma protein; Retinoblastoma Protein - metabolism; triptolide; Tumor Cells, Cultured; Tumors
• ISSN: 0167-594X; 1573-7373
• DOI: 10.1007/s11060-012-0885-5

Malignant glioma is the most devastating and aggressive tumor in brain, characterized by rapid proliferation and diffuse invasion. Chemotherapy and radiotherapy are the pivotal strategies after surgery; however, high drug resistance of malignant glioma and the blood–brain barrier usually render chemotherapy drugs ineffective. Here, we find that triptolide, a small molecule with high lipid solubility, is capable of inhibiting proliferation and invasion of malignant glioma cells effectively. In both investigated malignant glioma cell lines, triptolide repressed cell proliferation via inducing cell cycle arrest in G0/G1 phase, associated with downregulation of G0/G1 cell cycle regulators cyclin D1, CDK4, and CDK6 followed by reduced phosphorylation of retinoblastoma protein (Rb). In addition, triptolide induced morphological change of C6 cells through downregulation of protein expression of MAP-2 and inhibition of activities of GTPases Cdc42 and Rac1/2/3, thus significantly suppressing migratory and invasive capacity. Moreover, in an in vivo tumor model, triptolide delayed growth of malignant glioma xenografts. These findings suggest an important inhibitory action of triptolide on proliferation and invasion of malignant glioma, and encourage triptolide as a candidate for glioma therapy.