Ethanol extract of Vanilla planifolia stems reduces PAK6 expression and induces cell death in glioblastoma cells

Author:

Chang Hui Hua1234,Chang Alice Y. W.5,Tsai Bing‐Chen5,Chen Yu‐Ju6,Wu Sung‐Ghun6,Chen Li‐Jyun7,Lin Yi‐Xuan6,Hsueh Yuan‐Shuo8910ORCID

Affiliation:

1. Institute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University Tainan Taiwan

2. School of Pharmacy, College of Medicine National Cheng Kung University Tainan Taiwan

3. Department of Pharmacy National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University Tainan Taiwan

4. Department of Pharmacy National Cheng Kung University Hospital, Dou‐Liou Branch Yunlin Taiwan

5. Department of Physiology, College of Medicine National Cheng Kung University Tainan Taiwan

6. Department of Medical Science Industries, College of Health Sciences Chang Jung Christian University Tainan Taiwan

7. Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University Kaohsiung Taiwan

8. Department of Physiology, School of Post Baccalaureate Medicine, College of Medicine Kaohsiung Medical University Kaohsiung Taiwan

9. Center for Cancer Research Kaohsiung Medical University Kaohsiung Taiwan

10. Department of Medical Research Kaohsiung Medical University Hospital Kaohsiung Taiwan

Abstract

AbstractGlioblastoma multiforme (GBM) is a malignant tumour with a poor prognosis. Therefore, potential treatment strategies and novel therapeutic targets have gained increased attention. Our data showed that the ethanol extract of Vanilla planifolia stem (VAS) significantly decreased the viability and the colony formation of GBM cells. Moreover, VAS induced the cleavage of MAP1LC3, a marker of autophagy. Further RNA‐seq and bioinformatic analysis revealed 4248 differentially expressed genes (DEGs) between VAS‐treated GBM cells and the control cells. Protein–protein interactions between DEGs with fold changes less than −3 and more than 5 were further analysed, and we found that 16 and 9 hub DEGs, respectively, were correlated with other DEGs. Further qPCR experiments confirmed that 14 hub DEGs was significantly downregulated and 9 hub DEGs was significantly upregulated. In addition, another significantly downregulated DEG, p21‐activated kinase 6 (PAK6), was correlated with the overall survival of GBM patients. Further validation experiments confirmed that VAS significantly reduced the mRNA and protein expression of PAK6, which led to the abolition of cell viability and colony formation. These findings demonstrated that VAS reduced cell viability, suppressed colony formation and induced autophagy and revealed PAK6 and other DEGs as potential therapeutic targets for GBM treatment.

Funder

Kaohsiung Medical University

National Science and Technology Council

National Cheng Kung University Hospital

Publisher

Wiley

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