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


METHODS
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.
Tsai
Nu-Man
NM
Institute of Medical Sciences, Buddhist Tzu Chi University, Hualien, Taiwan, ROC.
Lin
Shinn-Zong
SZ
Lee
Chau-Chin
CC
Chen
Shee-Ping
SP
Su
Hsuan-Chi
HC
Chang
Wen-Liang
WL
Harn
Horng-Jyh
HJ
D029971:Angelica sinensis; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D041702:BALB 3T3 Cells; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D053148:Caspase 3; D053181:Caspase 8; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002725:Chloroform; D004789:Enzyme Activation / Q000187:drug effects; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology; D018922:HL-60 Cells; D006801:Humans; D020287:In Situ Nick-End Labeling; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D051379:Mice; D008819:Mice, Nude; D010766:Phosphorylation / Q000187:drug effects; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D011916:Rats, Inbred F344; D016160:Retinoblastoma Protein / Q000378:metabolism; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D019394:Ki-67 Antigen; D010936:Plant Extracts; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D002725:Chloroform; C505407:CASP3 protein, human; C505530:CASP8 protein, human; C505409:Casp3 protein, mouse; C505410:Casp3 protein, rat; C505526:Casp8 protein, mouse; C505528:Casp8 protein, rat; D053148:Caspase 3; D053181:Caspase 8; D020169:Caspases