The Methanol Extract of Angelica sinensis Induces Cell Apoptosis and Suppresses Tumor Growth in Human Malignant Brain Tumors

Glioblastoma multiforme (GBM) is a highly vascularized and invasive neoplasm. 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.

[1]  Susan M. Chang,et al.  Phase I/II study of sorafenib in combination with temsirolimus for recurrent glioblastoma or gliosarcoma: North American Brain Tumor Consortium study 05-02. , 2012, Neuro-oncology.

[2]  E. Chiocca,et al.  Anti-angiogenic gene therapy in the treatment of malignant gliomas , 2012, Neuroscience Letters.

[3]  J. Baehring,et al.  Glioblastoma multiforme: overview of current treatment and future perspectives. , 2012, Hematology/oncology clinics of North America.

[4]  M. Chamberlain Role for cytotoxic chemotherapy in patients with recurrent glioblastoma progressing on bevacizumab: a retrospective case series , 2012, Expert review of neurotherapeutics.

[5]  R. Bjerkvig,et al.  Molecular mechanisms of temozolomide resistance in glioblastoma multiforme , 2012, Expert review of anticancer therapy.

[6]  Q. Mei,et al.  Antivirus and immune enhancement activities of sulfated polysaccharide from Angelica sinensis. , 2012, International journal of biological macromolecules.

[7]  H. Harn,et al.  Induction of Apoptosis Coupled to Endoplasmic Reticulum Stress in Human Prostate Cancer Cells by n-butylidenephthalide , 2012, PloS one.

[8]  M. von Knebel Doeberitz,et al.  Phase I/IIa study of intratumoral/intracerebral or intravenous/intracerebral administration of Parvovirus H-1 (ParvOryx) in patients with progressive primary or recurrent glioblastoma multiforme: ParvOryx01 protocol , 2012, BMC Cancer.

[9]  Jun Wang,et al.  Ferulic acid promotes endothelial cells proliferation through up-regulating cyclin D1 and VEGF. , 2011, Journal of ethnopharmacology.

[10]  H. Chiu,et al.  Effects of a Chinese medical herbs complex on cellular immunity and toxicity-related conditions of breast cancer patients , 2011, British Journal of Nutrition.

[11]  H. Harn,et al.  Butylidenephthalide Suppresses Human Telomerase Reverse Transcriptase (TERT) in Human Glioblastomas , 2011, Annals of Surgical Oncology.

[12]  D. Charnock-Jones,et al.  The natural compound n-butylidenephthalide derived from the volatile oil of Radix Angelica sinensis inhibits angiogenesis in vitro and in vivo , 2011, Angiogenesis.

[13]  J. Ge,et al.  Extraction, chemical analysis of Angelica sinensis polysaccharides and antioxidant activity of the polysaccharides in ischemia-reperfusion rats. , 2010, International journal of biological macromolecules.

[14]  Yizeng Liang,et al.  Chemical composition and inhibitory effect on hepatic fibrosis of Danggui Buxue Decoction. , 2010, Fitoterapia.

[15]  José Weber Vieira de Faria,et al.  Treatment of recurrent glioblastoma with intra-arterial BCNU [1, 3-bis (2-chloroethyl)-1-nitrosourea]. , 2010, Arquivos de neuro-psiquiatria.

[16]  J. Hainsworth,et al.  Concurrent radiotherapy and temozolomide followed by temozolomide and sorafenib in the first‐line treatment of patients with glioblastoma multiforme , 2010, Cancer.

[17]  B. Zhivotovsky,et al.  Mitochondrial regulation of cell death: processing of apoptosis-inducing factor (AIF). , 2010, Biochemical and biophysical research communications.

[18]  Sarah Zohar,et al.  Intracerebral administration of CpG oligonucleotide for patients with recurrent glioblastoma: a phase II study. , 2010, Neuro-oncology.

[19]  R. Nishikawa [Treatment of glioma with temozolomide]. , 2009, Brain and nerve = Shinkei kenkyu no shinpo.

[20]  Jun-Rong Du,et al.  Z-ligustilide extracted from Radix Angelica Sinensis decreased platelet aggregation induced by ADP ex vivo and arterio-venous shunt thrombosis in vivo in rats. , 2009, Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan.

[21]  H. Maximilian Mehdorn,et al.  Localized BCNU chemotherapy and the multimodal management of malignant glioma , 2009 .

[22]  H. Mehdorn,et al.  Localized BCNU chemotherapy and the multimodal management of malignant glioma. , 2009, Current medical research and opinion.

[23]  Santosh Kesari,et al.  Malignant gliomas in adults. , 2008, The New England journal of medicine.

[24]  Y. Xin,et al.  Angelica sinensis: a novel adjunct to prevent doxorubicin-induced chronic cardiotoxicity. , 2007, Basic & clinical pharmacology & toxicology.

[25]  M. Pitt,et al.  The effectiveness and cost-effectiveness of carmustine implants and temozolomide for the treatment of newly diagnosed high-grade glioma: a systematic review and economic evaluation. , 2007, Health technology assessment.

[26]  K. Bae,et al.  Cytotoxic constituents from Angelicae Sinensis radix , 2007, Archives of pharmacal research.

[27]  P. Wen,et al.  Glioma Therapy in Adults , 2006, The neurologist.

[28]  H. Harn,et al.  The natural compound n-butylidenephthalide derived from Angelica sinensis inhibits malignant brain tumor growth in vitro and in vivo3 , 2006, Journal of neurochemistry.

[29]  Z. Qian,et al.  Neuroprotective role of Z-ligustilide against forebrain ischemic injury in ICR mice , 2006, Brain Research.

[30]  F. Occhiuto,et al.  Estrogenic activity of standardized extract of Angelica sinensis , 2006, Phytotherapy research : PTR.

[31]  Tutut Herawan,et al.  Computational and mathematical methods in medicine. , 2006, Computational and mathematical methods in medicine.

[32]  J. Sung,et al.  Anti-proliferative and pro-apoptotic effects of herbal medicine on hepatic stellate cell. , 2005, Journal of ethnopharmacology.

[33]  B. Scheithauer,et al.  Phase II trial of temsirolimus (CCI-779) in recurrent glioblastoma multiforme: a North Central Cancer Treatment Group Study. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[34]  Susan M. Chang,et al.  Phase II study of CCI-779 in patients with recurrent glioblastoma multiforme , 2005, Investigational New Drugs.

[35]  H. Harn,et al.  The Antitumor Effects of Angelica sinensis on Malignant Brain Tumors In vitro and In vivo , 2005, Clinical Cancer Research.

[36]  H. Harn,et al.  Acetone extract of Angelica sinensis inhibits proliferation of human cancer cells via inducing cell cycle arrest and apoptosis. , 2004, Life sciences.

[37]  C. Cho,et al.  Effect of polysaccharides from Angelica sinensis on gastric ulcer healing. , 2003, Life sciences.

[38]  B. Kaplan,et al.  The immediate effect of natural plant extract, Angelica sinensis and Matricaria chamomilla (Climex) for the treatment of hot flushes during menopause. A preliminary report. , 2003, Clinical and experimental obstetrics & gynecology.

[39]  Y. Fang,et al.  Interplays between genetic and environmental mechanisms trigger tumorigenic VEGF signalling in human HCC cell lines: pilot study. , 2002, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[40]  H. Avraham,et al.  VEGF165 requires extracellular matrix components to induce mitogenic effects and migratory response in breast cancer cells , 2001, Oncogene.

[41]  C. Cho,et al.  Protective effect of polysaccharides-enriched fraction from Angelica sinensis on hepatic injury. , 2001, Life sciences.

[42]  H. Matsui,et al.  A mechanistic study of proliferation induced by Angelica sinensis in a normal gastric epithelial cell line. , 2001, Biochemical pharmacology.

[43]  H. Matsui,et al.  Angelica sinensis modulates migration and proliferation of gastric epithelial cells. , 2001, Life sciences.

[44]  C. Cho,et al.  Study of the gastrointestinal protective effects of polysaccharides from Angelica sinensis in rats. , 2000, Planta medica.

[45]  James M. Roberts,et al.  Inhibitors of mammalian G1 cyclin-dependent kinases. , 1995, Genes & development.

[46]  P F Morrison,et al.  Convection-enhanced delivery of macromolecules in the brain. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[47]  Ludger Hengst,et al.  G1 control in mammalian cells , 1994, Journal of Cell Science.

[48]  A. Levine,et al.  Tumor-suppressor p53 and the cell cycle. , 1993, Current opinion in genetics & development.