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

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Abstract

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.

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Acknowledgments

The study was supported by the National Natural Science Foundation of China No.81471212, 81271275, 81070947, and 30770759 to B.-L. Sun and Natural Science Foundation of Shandong No. ZR2012HZ006 to B.-L. Sun.

Conflict of interest

The authors declare that there is no conflict of interest for all the authors.

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Authors and Affiliations

  1. Department of Chemistry, Jinan University, Guangzhou, 510632, China

    Xiao-yan Fu

  2. School of Basic Medicine, Taishan Medical University, Taian, 271000, Shandong, China

    Xiao-yan Fu

  3. Key Lab of Cerebral Microcirculation in Universities of Shandong, Taishan Medical University, Taian, 271000, Shandong, China

    Xiao-yan Fu, Shuai Zhang, Ming-feng Yang, Cun-dong Fan & Bao-liang Sun

  4. Taishan Vocational College of Nursing, Taian, 271000, Shandong, China

    Kun Wang

  5. Affiliated Hospital of Taishan Medical University, Taian, 271000, Shandong, China

    Bao-liang Sun

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  1. Xiao-yan Fu
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  2. Shuai Zhang
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  3. Kun Wang
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  4. Ming-feng Yang
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  5. Cun-dong Fan
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Correspondence to Xiao-yan Fu, Cun-dong Fan or Bao-liang Sun.

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Xiao-yan Fu and Shuai Zhang are co-first authors.

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Fu, Xy., Zhang, S., Wang, K. et al. Caudatin Inhibits Human Glioma Cells Growth Through Triggering DNA Damage-Mediated Cell Cycle Arrest. Cell Mol Neurobiol 35, 953–959 (2015). https://doi.org/10.1007/s10571-015-0190-x

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