穿心莲内酯通过ERK-p53-半胱天冬酶7-PARP途径诱导C6胶质瘤细胞凋亡。

Andrographolide induces apoptosis of C6 glioma cells via the ERK-p53-caspase 7-PARP pathway.

作者信息

Yang Shih-Hung, Wang Seu-Mei, Syu Jhih-Pu, Chen Ying, Wang Sheng-De, Peng Yu-Sen, Kuo Meng-Fai, Kung Hsiu-Ni

机构信息

Division of Neurosurgery, Department of Surgery, National Taiwan University Hospital, No. 7, Zhongshan South Road, Zhongzheng District, Taipei City 100, Taiwan.

Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, 1-1 Jen-Ai Road, Taipei 10051, Taiwan.

出版信息

Biomed Res Int. 2014;2014:312847. doi: 10.1155/2014/312847. Epub 2014 Aug 5.

BACKGROUND

Glioma is the most malignant tumor of the central nervous system. Efforts on the development of new chemotherapy are mandatory. Andrographolide (AND), a diterpenoid lactone isolated from the Andrographis paniculata, has been shown to have antitumor activities in several types of cancer cells. Whether AND can exert its antitumor activity in glioblastoma cells remains unknown. This study examined the anticancer effects of AND, both in vitro and in vivo.

METHODS

Cell apoptosis was assayed by flow cytometry and nuclear staining. The signaling pathway for AND was determined by western blotting. The effects of AND on tumor growth was evaluated in a mouse model.

RESULTS AND CONCLUSION

In vitro, with application of specific inhibitors and siRNA, AND-induced apoptosis was proven through ROS-ERK-P53-caspase 7-PARP signaling pathway. In vivo, AND significantly retarded tumor growth and caused regression of well-formed tumors in vivo. Furthermore, AND did not induce apoptosis or activate ERK and p53 in primary cultured astrocyte cells, and it may serve as a potential therapeutic candidate for the treatment of glioma.