The antitumor effects of Angelica sinensis on malignant brain tumors in vitro and in vivo.

Abstract

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.

• Authors: Nu-Man Tsai, Shinn-Zong Lin, Chau-Chin Lee, Shee-Ping Chen, Hsuan-Chi Su, Wen-Liang Chang, Horng-Jyh Harn
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 11 Issue 9 Pg. 3475-84 (May 01 2005) ISSN: 1078-0432 [Print] United States
• PMID: 15867250 (Publication Type: Journal Article)

Chemical References

• Ki-67 Antigen
• Plant Extracts
• Retinoblastoma Protein
• Tumor Suppressor Protein p53
• Chloroform
• CASP3 protein, human
• CASP8 protein, human
• Casp3 protein, mouse
• Casp3 protein, rat
• Casp8 protein, mouse
• Casp8 protein, rat
• Caspase 3
• Caspase 8
• Caspases

Topics

• Angelica sinensis
• Animals
• Apoptosis (drug effects)
• BALB 3T3 Cells
• Brain Neoplasms (drug therapy, pathology)
• Caspase 3
• Caspase 8
• Caspases (metabolism)
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Chloroform
• Enzyme Activation (drug effects)
• Glioblastoma (drug therapy, pathology)
• HL-60 Cells
• Humans
• In Situ Nick-End Labeling
• Ki-67 Antigen (metabolism)
• Male
• Mice
• Mice, Nude
• Phosphorylation (drug effects)
• Phytotherapy
• Plant Extracts (isolation & purification, pharmacology, therapeutic use)
• Rats
• Rats, Inbred F344
• Retinoblastoma Protein (metabolism)
• Time Factors
• Tumor Suppressor Protein p53 (metabolism)
• Xenograft Model Antitumor Assays