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Plumbagin induces growth inhibition of human glioma cells by downregulating the expression and activity of FOXM1

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Abstract

Plumbagin, a natural quinonoid constituent isolated from the root of medicinal plant Plumbago zeylanica L, has exhibited anti-tumor and anti-proliferative activities in various tumor cell lines as well as in animal tumor models. However, its anticancer effects and the mechanisms underlying its suppression of glioma cell growth have not been elucidated. Oncogenic transcription factor Forkhead Box M1 (FOXM1) has garnered particular interest in recent years as a potential target for the prevention and/or therapeutic intervention in glioma, nevertheless, less information is currently available regarding FOXM1 inhibitor. Here, we reported that plumbagin could effectively inhibit cell proliferation, migration and invasion and induce apoptosis of glioma cells. Cell cycle assay showed that plumbagin induced G2/M arrest. Interestingly, we found that plumbagin decreased the expression of FOXM1 both at mRNA level and protein level. Plumbagin also inhibited the transactivation ability of FOXM1, resulting in down-regulating the expression of FOXM1 downstream target genes, such as cyclin D1, Cdc25B, survivin, and increasing the expression of p21CIP1 and p27KIP1. Most importantly, down-regulation of FOXM1 by siFOXM1 transfection enhanced plumbagin-induced change in viability. On the contrary, over-expression of FOXM1 by cDNA transfection reduced plumbagin-induced glioma cell growth inhibition. These results suggest that plumbagin exhibits its anticancer activity partially by inactivation of FOXM1 signaling pathway in glioma cells. Our findings indicate that plumbagin may be considered as a potential natural FOXM1 inhibitor, which could contribute to the development of new anticancer agent for therapy of gliomas.

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Acknowledgments

The research was supported by National Natural Science Foundation of China (Nos. 81402074; 81472345; 81400167);Natural Science Foundation of Jiangsu province (No. BK20140224; No. BK20140227);Natural Science Foundation of the Jiangsu Higher Education Institutions of China (No. 14KJB320022).

Conflict of interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Institute of Nervous System Diseases, Xuzhou Medical College, Xuzhou, Jiangsu, China

    Xuejiao Liu, Wei Cai, Yulong Chong, Huize Liu, Wenqiang Hu, Dacheng Wang, Shangfeng Gao, Qiong Shi, Jinxia Hu, Xiuping Zhou & Rutong Yu

  2. Brain Hospital, Affiliated Hospital of Xuzhou Medical College, 99 West Huai-hai Road, Xuzhou, 221002, Jiangsu, China

    Xuejiao Liu, Shangfeng Gao, Qiong Shi, Jinxia Hu, Xiuping Zhou & Rutong Yu

  3. The Graduate School, Xuzhou Medical College, Xuzhou, Jiangsu, China

    Wei Cai, Yulong Chong, Huize Liu, Wenqiang Hu & Dacheng Wang

  4. Blood Diseases Institute, Xuzhou Medical College, Xuzhou, Jiangsu, China

    Mingshan Niu

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  1. Xuejiao Liu
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  2. Wei Cai
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  9. Qiong Shi
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Correspondence to Rutong Yu.

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Xuejiao Liu and Wei Cai have contributed equally to this work.

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Liu, X., Cai, W., Niu, M. et al. Plumbagin induces growth inhibition of human glioma cells by downregulating the expression and activity of FOXM1. J Neurooncol 121, 469–477 (2015). https://doi.org/10.1007/s11060-014-1664-2

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  • DOI: https://doi.org/10.1007/s11060-014-1664-2

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