4.5 Article

Triptolide inhibits proliferation and invasion of malignant glioma cells

Journal

JOURNAL OF NEURO-ONCOLOGY
Volume 109, Issue 1, Pages 53-62

Publisher

SPRINGER
DOI: 10.1007/s11060-012-0885-5

Keywords

Triptolide; Malignant glioma; Proliferation; Cell cycle; Invasion

Funding

  1. National Natural Science Foundation of China [30830111]
  2. Guangdong Natural Science Foundation [S2011040004371]
  3. China Postdoctoral Science Foundation [20100480824]

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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.

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