TY - JOUR
T1 - Triptolide inhibits proliferation and invasion of malignant glioma cells
AU - Zhang, Haipeng
AU - Zhu, Wenbo
AU - Su, Xingwen
AU - Wu, Sihan
AU - Lin, Yuan
AU - Li, Jingjie
AU - Wang, Youqiong
AU - Chen, Jingkao
AU - Zhou, Yuxi
AU - Qiu, Pengxin
AU - Yan, Guangmei
AU - Zhao, Shujin
AU - Hu, Jun
AU - Zhang, Jingxia
N1 - Funding Information:
Acknowledgments This work was supported by Key Program, National Natural Science Foundation of China (30830111), Guangdong Natural Science Foundation (S2011040004371), and China Postdoctoral Science Foundation (20100480824).
PY - 2012/8
Y1 - 2012/8
N2 - 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.
AB - 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.
KW - Cell cycle
KW - Invasion
KW - Malignant glioma
KW - Proliferation
KW - Triptolide
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U2 - 10.1007/s11060-012-0885-5
DO - 10.1007/s11060-012-0885-5
M3 - Article
C2 - 22562416
AN - SCOPUS:84864279690
SN - 0167-594X
VL - 109
SP - 53
EP - 62
JO - Journal of Neuro-Oncology
JF - Journal of Neuro-Oncology
IS - 1
ER -