Document Type : Research Articles
Authors
1
Department of Physiology, Faculty of Science, Mahidol University, Bangkok, Thailand.
2
Princess Srisavangavadhana College of Medicine, Chulabhorn Royal Academy, Bangkok, Thailand.
3
Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangpla, Bangpli, Samutprakarn, Thailand.
4
School of Bioinnovation and Bio-based Product Intelligence, Faculty of Science, Mahidol University, Bangkok, Thailand.
5
Excellent Center for Drug Discovery (ECDD), Faculty of Science, Mahidol University, Bangkok, Thailand.
6
6Department of Chemistry, Faculty of Science, Mahidol University, Bangkok, Thailand.
7
Center for Neuroscience, Faculty of Science, Mahidol University, Bangkok, Thailand.
Abstract
Objective: Glioblastoma is the most aggressive and lethal brain tumor in adults with highly invasive properties. In this present study, we explored the effects of Phyllanthus taxodiifolius Beille extract on molecules known to be hallmarks of aggressive glioblastoma including N-cadherin and vimentin, mesenchymal markers, as well as paxillin, a major adaptor protein that regulates the linking of focal adhesions to the actin cytoskeleton. Methods: P. taxodiifolius were air-dried, powdered and percolated with methanol, filtered, concentrated and lyophilized to yield a crude methanol extract. C6 glioblastoma cell line was used in this study. The expression of N-cadherin and vimentin, as well as the activation of paxillin was determined using Western blot analysis. The effect of the extract on focal adhesions and actin cytoskeleton were investigated using immunofluorescence staining and confocal imaging. Results: In the presence of 40 µg/ml Phyllanthus taxodiifolius Beille extract, the expression of N-cadherin and vimentin were significantly decreased (p<0.001 and p<0.05, respectively). Activation of paxillin was also diminished as indicated by a reduction of phosphorylated-paxillin (p<0.01). Consequently, actin stress fibers in glioblastoma cells were abolished as evidenced by the decrease in focal adhesion (p<0.001) and stress fibers numbers (p<0.001). Conclusion: Our study demonstrates for the first time that P. taxodiifolius interferes with multiple key molecules related to pathological hallmarks of glioblastoma. These molecules are involved with cell contacts, focal adhesions, and the formation and stabilization of actin stress fibers, which are required for glioblastoma metastatic behavior. These results provide further evidence supporting the potential of P. taxodiifolius and its bioactive compounds as anti-cancer agents.
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