Triptolide inhibits proliferation and invasion of malignant glioma cells.

Abstract

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.

• Authors: Haipeng Zhang, Wenbo Zhu, Xingwen Su, Sihan Wu, Yuan Lin, Jingjie Li, Youqiong Wang, Jingkao Chen, Yuxi Zhou, Pengxin Qiu, Guangmei Yan, Shujin Zhao, Jun Hu, Jingxia Zhang
• Journal: Journal of neuro-oncology (J Neurooncol) Vol. 109 Issue 1 Pg. 53-62 (Aug 2012) ISSN: 1573-7373 [Electronic] United States
• PMID: 22562416 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Alkylating
• Diterpenes
• Epoxy Compounds
• Phenanthrenes
• Retinoblastoma Protein
• triptolide
• Cyclin-Dependent Kinases
• Rac1 protein, rat
• cdc42 GTP-Binding Protein
• rac GTP-Binding Proteins
• rac1 GTP-Binding Protein

Topics

• Animals
• Antineoplastic Agents, Alkylating (pharmacology)
• Apoptosis (drug effects)
• Blotting, Western
• Brain Neoplasms (drug therapy, metabolism, pathology)
• Cell Cycle (drug effects)
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Cyclin-Dependent Kinases (metabolism)
• Diterpenes (pharmacology)
• Epoxy Compounds (pharmacology)
• Female
• Flow Cytometry
• Glioma (drug therapy, metabolism, pathology)
• Mice
• Mice, Nude
• Neoplasm Invasiveness
• Phenanthrenes (pharmacology)
• Rats
• Retinoblastoma Protein (metabolism)
• Tumor Cells, Cultured
• cdc42 GTP-Binding Protein (metabolism)
• rac GTP-Binding Proteins (metabolism)
• rac1 GTP-Binding Protein (metabolism)
• RAC2 GTP-Binding Protein