Angelica sinensis Extract Induces Telomere Dysfunction, Cell Cycle Arrest, and Mitochondria-Mediated Apoptosis in Human Glioblastoma Cells

Author:

Ma Tsung-Liang1,Chang Kai-Fu2,Huang Xiao-Fan2,Lai Hung-Chih34,Hsiao Chih-Yen1,Tsai Nu-Man256

Affiliation:

1. Division of Nephrology, Department of Internal Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan

2. Department of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan

3. Division of Hematology and Oncology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital

4. Institute of Pharmacology, National Taiwan University, Taipei, Taiwan

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

6. Department of Life-and-Death Studies, Nanhua University, Chiayi, Taiwan

Abstract

Glioblastoma (GB) is one of the most aggressive and malignant tumors of the central nervous system. Conventional treatment for GB requires surgical resection followed by radiotherapy combined with temozolomide chemotherapy; however, the median survival time is only 12–15 months. Angelica sinensis Radix (AS) is commonly used as a traditional medicinal herb or a food/dietary supplement in Asia, Europe, and North America. This study aimed to investigate the effect of AS-acetone extract (AS-A) on the progression of GB and the potential mechanisms underlying its effects. The results indicated that AS-A used in this study showed potency in growth inhibition of GB cells and reduction of telomerase activity. In addition, AS-A blocked the cell cycle at the G0/G1 phase by regulating the expression of p53 and p16. Furthermore, apoptotic morphology, such as chromatin condensation, DNA fragmentation, and apoptotic bodies, was observed in AS-A-treated cells, induced by the activation of the mitochondria-mediated pathway. In an animal study, AS-A reduced tumor volume and prolonged lifespans of mice, with no significant changes in body weight or obvious organ toxicity. This study confirmed the anticancer effects of AS-A by inhibiting cell proliferation, reducing telomerase activity, altering cell cycle progression, and inducing apoptosis. These findings suggest that AS-A has great potential for development as a novel agent or dietary supplement against GB.

Publisher

Medknow

Subject

Physiology (medical),Physiology

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