Journal
INTERNATIONAL JOURNAL OF MEDICAL SCIENCES
Volume 18, Issue 11, Pages 2417-2430Publisher
IVYSPRING INT PUBL
DOI: 10.7150/ijms.54468
Keywords
Glioblastoma; Cedrus atlantica; DNA damage; cell apoptosis; drug combination
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Funding
- Ministry of Science and Technology, Taiwan [MOST 105-2320-B-040-025, MOST 109-2320-B-040-012]
- Chung Shan Medical University Hospital Foundation, Taiwan [CSH-2013-A-025, CSH-2014-A-019]
- Ditmanson Medical Foundation Chia-Yi Christian Hospital, Taiwan [R110-01]
- National Science Council
- Ministry of Education
- Chung Shan Medical University
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The research demonstrated the anti-glioblastoma activity of Cedrus atlantica (CAt) extract by increasing ROS levels, inducing DNA damage, inducing G(0)/G(1) cell cycle arrest, and cell apoptosis. Additionally, CAt extract also suppresses GBM growth by regulating protein expression and activating apoptosis.
Glioblastoma (GBM) is the most common malignant primary brain tumor in humans, exhibiting highly infiltrative growth and drug resistance to conventional chemotherapy. Cedrus atlantica (CAt) extract has been shown to decrease postoperative pain and inhibit the growth of K562 leukemia cells. The aim of this study was to assess the anti-GBM activity and molecular mechanism of CAt extract in vitro and in vivo. The results showed that CAt extract greatly suppressed GBM cells both in vitro and in vivo and enhanced the survival rate in subcutaneous and orthotopic animal models. Moreover, CAt extract increased the level of ROS and induced DNA damage, resulting in cell cycle arrest at the G(0)/G(1) phase and cell apoptosis. Western blotting results indicated that CAt extract regulates p53/p21 and CDK4/cyclin D1 protein expression and activates extrinsic and intrinsic apoptosis. Furthermore, CAt extract enhanced the cytotoxicity of Temozolomide and decreased AKT/mTOR signaling by combination treatment. In toxicity assays, CAt extract exhibited low cytotoxicity toward normal cells or organs in vitro and in vivo. CAt extract suppresses the growth of GBM by induction of genotoxicity and activation of apoptosis. The results of this study suggest that CAt extract can be developed as a therapeutic agent or adjuvant for GBM treatment in the future.
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