Caudatin Inhibits Human Glioma Cells Growth Through Triggering DNA Damage-Mediated Cell Cycle Arrest

Caudatin, one of the species of C-21 steroidal glycosides mainly isolated from the root of Cynanchum bungei Decne , exhibits potent anticancer activities. However, the mechanism remains poorly defined. In the present study, the growth inhibitory effect and mechanism of caudatin on human glioma cells...

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Bibliographic Details
Published in:Cellular and molecular neurobiology 2015-10, Vol.35 (7), p.953-959
Main Authors: Fu, Xiao-yan, Zhang, Shuai, Wang, Kun, Yang, Ming-feng, Fan, Cun-dong, Sun, Bao-liang
Format: Article
Language:English
Subjects:
Biomedical and Life Sciences
Biomedicine
Cell Biology
Cell Cycle Checkpoints - drug effects
Cell Cycle Checkpoints - physiology
Cell Line, Tumor
DNA Damage - drug effects
DNA Damage - physiology
Dose-Response Relationship, Drug
Glioma - drug therapy
Glioma - metabolism
Glycosides - chemistry
Glycosides - pharmacology
Glycosides - therapeutic use
Growth Inhibitors - pharmacology
Growth Inhibitors - therapeutic use
Humans
Neurobiology
Neurosciences
Original Research
Steroids - chemistry
Steroids - pharmacology
Steroids - therapeutic use
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Summary:Caudatin, one of the species of C-21 steroidal glycosides mainly isolated from the root of Cynanchum bungei Decne , exhibits potent anticancer activities. However, the mechanism remains poorly defined. In the present study, the growth inhibitory effect and mechanism of caudatin on human glioma cells were evaluated in vitro. The results revealed that caudatin time- and dose-dependently inhibited U251 and U87 cells growth. Flow cytometry analysis indicated that caudatin-induced growth inhibition against U251 and U87 cells was mainly achieved by the induction of G0/G1 and S-phase cell cycle arrest through triggering DNA damage, as convinced by the up-regulation of p53, p21, and histone phosphorylation, as well as the down-regulation of cyclin D1. Moreover, caudatin treatment also triggered the activation of ERK and inactivation of AKT pathway. LY294002 (an AKT inhibitor) addition enhanced caudation-induced AKT inhibition, indicating that caudatin inhibited U251 cells growth in an AKT-dependent manner. Taken together, these results indicate that caudatin may act as a novel cytostatic reagent against human glioma cells through the induction of DNA damage-mediated cell cycle arrest with the involvement of modulating MAPK and AKT pathways.
ISSN:0272-4340
1573-6830
DOI:10.1007/s10571-015-0190-x