Cancer: Glioblastoma
Action: Cell-cycle arrest
Glioblastoma multiforme (GBM), the most common malignant tumor of the central nervous system, is a highly vascularized and invasive neoplasm. The annual incidence of GBM was approximately 5–7 per 100,000 people per year in the USA between 1995 and 2008. Because of its malignant properties, rapid growth, diffuse invasion, and resistance to current therapies, the median survival of GBM patients is approximately 50 weeks. Current treatments combine surgery, radiation, and chemoradiotherapy, providing an increase in the median overall survival from 12 to 15 months.
The methanol extract of Angelica sinensis (AS-M) is commonly used in traditional Chinese medicine to treat several diseases, such as gastric mucosal damage, hepatic injury, menopausal symptoms, and chronic glomerulonephritis. AS-M also displays potency in suppressing the growth of malignant brain tumor cells. The growth suppression of malignant brain tumor cells by AS-M results from cell cycle arrest and apoptosis.
AS-M upregulates expression of cyclin kinase inhibitors, including p16, to decrease the phosphorylation of Rb proteins, resulting in arrest at the G0-G1 phase. The expression of the p53 protein is increased by AS-M and correlates with activation of apoptosis-associated proteins. Therefore, the apoptosis of cancer cells induced by AS-M may be triggered through the p53 pathway. In in vivo studies, AS-M not only suppresses the growth of human malignant brain tumors but also significantly prolongs patient survival.
In addition, AS-M has potent anticancer effects involving cell cycle arrest, apoptosis, and antiangiogenesis. The in vitro and in vivo anticancer effects of AS-M indicate that this extract warrants further investigation and potential development as a new antibrain tumor agent, providing new hope for the chemotherapy of malignant brain cancer.
The different extracts of A. sinensis, such as water, chloroform, and acetone extracts, have demonstrated antitumor biofunctions (Cheng et al., 2004; Tsai et al., 2005). In this study, AS-M has demonstrated to be a potential antitumor extract isolated from A. sinensis that efficiently inhibits GBM tumor growth. In an in vitro cytotoxic assay, brain tumor cells were sensitive to AS-M and normal fibroblast cells were unsusceptible to AS-M. AS-M dramatically inhibited 90% of the subcutaneous tumor growth and prolonged survival in vivo. AS-M efficiently suppressed tumor growth by inducing cell cycle arrest at the G0-G1 phase and promoting apoptosis. The AS-M mechanism was found to involve the cyclin/CDK/CKI cell cycle regulatory system and the upregulation of p16 and p53 expression.
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