Acetone extract of Angelica sinensis inhibits proliferation of human cancer cells via inducing cell cycle arrest and apoptosis.
Angelica sinensis (Oliv.) Diels, a traditional Chinese medicine, has been widely prescribed in treatment of gynecological diseases. Bio-based assays for extracts of Angelica sinensis showed that the acetone extract (AE-AS) had dose-dependently antiproliferative effect on A549, HT29, DBTRG-05MG and J5 human cancer cells. The IC50 values of AE-AS on mentioned cancer cells ranged from 35 to 50 microg/ml after 24 h of treatment. After 72 h of exposure, AE-AS (40 microg/ml) significantly reduced A549 cell proliferation to 24 +/- 3.2% of control. In A549 cells, the cell cycle analysis showed that AE-AS induced a significant increase in the number of cells in G0/G1, with a concomitant decrease in the number of cells in S phase. AE-AS-induced chromatin changes and apoptosis of A549 cells were confirmed by Hoechst 33342 DNA staining and annexin V staining. A549 cells treated with AE-AS caused activation of caspase-9 and -3, and AE-AS-induced apoptosis could be inhibited by the broad-spectrum caspase inhibitor, z-VAD-fmk. The Western blot indicated the AE-AS-triggered apoptosis is mediated via suppression of Bcl-2 oncoprotein expression rather than p53 or Bax. Besides, AE-AS decreased the levels of cdk4 protein was observed. These results indicate that the AE-AS could induce G1/S arrest and activate the mechanism of apoptosis in human cancer cells. Extracts obtained from different methods of fractionation might possess distinct bioactivity. These results prompted us to further evaluate the in vivo anticancer effects and elucidate the chemical composition profile of AE-AS.
Cheng
Yeung-Leung
YL
School of Pharmacy, National Defense Medical Center, Taipei 114, Taiwan, ROC.
Chang
Wen-Liang
WL
Lee
Shih-Chun
SC
Liu
Yau-Gye
YG
Chen
Cheng-Jueng
CJ
Lin
Shinn-Zong
SZ
Tsai
Nu-Man
NM
Yu
Dah-Shyong
DS
Yen
Chung-Yang
CY
Harn
Horng-Jyh
HJ
D000096:Acetone; D000590:Amino Acid Chloromethyl Ketones / Q000378:metabolism / Q000494:pharmacology; D029969:Angelica / Q000737:chemistry*; D017304:Annexin A5; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3; D053453:Caspase 9; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects*; D002843:Chromatin / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D019254:Genes, bcl-2 / Q000235:genetics; D006801:Humans; D007928:Lethal Dose 50; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000590:Amino Acid Chloromethyl Ketones; D017304:Annexin A5; D061945:Caspase Inhibitors; D002843:Chromatin; D004365:Drugs, Chinese Herbal; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D000096:Acetone; C505407:CASP3 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases