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The Antitumor Effects of Angelica sinensis on Malignant Brain Tumors In vitro and In vivo

Authors' Affiliations: ¹ Institute of Medical Sciences, Buddhist Tzu Chi University; ² Neuro-Medical Scientific Center and Departments of ³ Radiology and ⁴ Pathology, Buddhist Tzu Chi General Hospital, Hualien, Taiwan, ROC; and ⁵ School of Pharmacy, National Defense Medical Center, Taipei, Taiwan, ROC

Requests for reprints: Horng-Jyh Harn, Neuro-Medical Scientific Center, Department of Pathology, Tzu Chi General Hospital, 707, Section 3, Chung-Yang Road, 970 Hualien, Taiwan, ROC. Phone: 886-3-8561825, ext. 2223; Fax: 886-3-8564656; E-mail: duke{at}tzuchi.com.tw.

Purpose: In this study, we have examined the antitumor effects of chloroform extract of Angelica sinensis (AS-C), a traditional Chinese medicine, on glioblastoma multiforme (GBM) brain tumors in vitro and in vivo.

Experimental Design: In vitro, GBM cells were treated with AS-C, and the cell proliferation, changes in distributions of cell cycle, and apoptosis were determined. In vivo, human DBTRG-05MG and rat RG2 GBM tumor cells were injected s.c. or i.c. and were treated with AS-C. Effects on tumor growth were determined by tumor volume, magnetic resonance imaging, survival, and histology analysis.

Results: The AS-C displays potency in suppressing growth of malignant brain tumor cells without cytotoxicity to fibroblasts. Growth suppression of malignant brain tumor cells by AS-C results from cell cycle arrest and apoptosis. AS-C can up-regulate expression of cdk inhibitors, including p21, to decrease phosphorylation of Rb proteins resulting in cell arrest at the G₀-G₁ phase for DBTRG-05MG and RG2 cells. The apoptosis-associated proteins are dramatically increased and activated in DBTRG-05MG cells and RG2 cells by AS-C but RG2 cells without p53 protein expression. In vitro results showed AS-C triggered both p53-dependent and p53-independent pathways for apoptosis. In in vivo studies, AS-C not only can suppress growths of malignant brain tumors of rat and human origin but also shrink the volumes of in situ GBM, significantly prolonging survivals.

Conclusions: The in vitro and in vivo anticancer effects of AS-C indicate that it has sufficient potential to warrant further investigation and development as a new anti–brain tumor agent.

Key Words: Angelica sinensis • apoptosis • cell cycle arrest • glioblastoma multiformis (GBM) • chemotherapy

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