Research Papers:

Andrographolide suppresses the migratory ability of human glioblastoma multiforme cells by targeting ERK1/2-mediated matrix metalloproteinase-2 expression

Shih-Liang Yang, Fu-Hsuan Kuo, Pei-Ni Chen, Yi-Hsien Hsieh, Nuo-Yi Yu, Wei-En Yang, Ming-Ju Hsieh _ and Shun-Fa Yang

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Oncotarget. 2017; 8:105860-105872. https://doi.org/10.18632/oncotarget.22407

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Shih-Liang Yang1,2,*, Fu-Hsuan Kuo3,*, Pei-Ni Chen4,5, Yi-Hsien Hsieh4,5, Nuo-Yi Yu1, Wei-En Yang1,6, Ming-Ju Hsieh1,7,8 and Shun-Fa Yang1,6

1Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan

2Department of Traditional Chinese Medicine, Taichung Hospital, Ministry of Health and Welfare, Taichung, Taiwan

3Neurological Institute, Taichung Veterans General Hospital, Taichung, Taiwan

4Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung, Taiwan

5Clinical Laboratory, Chung Shan Medical University Hospital, Taichung, Taiwan

6Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan

7Cancer Research Center, Changhua Christian Hospital, Changhua, Taiwan

8Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan

*These authors have contributed equally to this work

Correspondence to:

Ming-Ju Hsieh, email: [email protected]

Shun-Fa Yang, email: [email protected]

Keywords: glioblastoma multiforme; andrographolide; migration; CREB

Received: September 08, 2017    Accepted: September 23, 2017    Published: November 11, 2017


Glioblastoma multiforme (GBM) can be a fatal tumor because of difficulties in treating the related metastasis. Andrographolide is the bioactive component of the Andrographis paniculata. Andrographolide possesses the anti-inflammatory activity and inhibits the growth of various cancers; however, its effect on GBM cancer motility remains largely unknown. In this study, we examined the antimetastatic properties of andrographolide in human GBM cells. Our results revealed that andrographolide inhibited the invasion and migration abilities of GBM8401 and U251 cells. Furthermore, andrographolide inhibited matrix metalloproteinase (MMP)-2 activity and expression. Real-time PCR and promoter activity assays indicated that andrographolide inhibited MMP-2 expression at the transcriptional level. Such inhibitory effects were associated with the suppression of CREB DNA-binding activity and CREB expression. Mechanistically, andrographolide inhibited the cell motility of GBM8401 cells through the extracellular-regulated kinase (ERK) 1/2 pathway, and the blocking of the ERK 1/2 pathway could reverse MMP-2-mediated cell motility. In conclusion, CREB is a crucial target of andrographolide for suppressing MMP-2-mediated cell motility in GBM cells. Therefore, a combination of andrographolide and an ERK inhibitor might be a good strategy for preventing GBM metastasis.

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