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Induction of apoptotic cell death by ursolic acid through mitochondrial death pathway and extrinsic death receptor pathway in MDA-MB-231 cells.
MedLine Citation:
PMID:  21910059     Owner:  NLM     Status:  In-Data-Review    
Ursolic acid (3-hydroxy-urs-12-en-28-oic acid) is a pentacyclic triterpenoid derived from leaves, berries, fruits, and flowers of medicinal plants, such as Rosemarinus officinalis. Ursolic acid has been shown to inhibit tumorigenesis, tumor promotion, and suppress angiogenesis. In our present study, we found that ursolic acid decreased cell proliferation rate and induce apoptosis in human breast cancer cell line, MDA-MB-231. When we checked the expression levels of proteins associated with apoptosis signal by using immunoblotting, we found that ursolic acid induces various apoptotic molecules related to either extrinsic or intrinsic apoptosis signal pathway in MDA-MB-231 cells. In our study, we found that ursolic acid induced the appearance of Fas receptor and cleavage of caspase-8, -3 and PARP. We also found that ursolic acid induced Bax up-regulation and Bcl-2 down-regulation and release of cytochrome C to the cytosol from mitochondria. Moreover, ursolic acid cleaved caspase-9 and decreased mitochondrial membrane potential (ΔΨm) as shown with JC-1 staining. These data indicate that ursolic acid induce apoptosis through both mitochondrial death pathway and extrinsic death receptor dependent pathway in MDA-MB-231 cells. Our data clearly indicate that ursolic acid could be used as a potential anticancer drug for breast cancer.
Kyung Hun Kim; Hye Sook Seo; Han Seok Choi; Inhwa Choi; Yong Cheol Shin; Seong-Gyu Ko
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Publication Detail:
Type:  Journal Article     Date:  2011-09-11
Journal Detail:
Title:  Archives of pharmacal research     Volume:  34     ISSN:  0253-6269     ISO Abbreviation:  Arch. Pharm. Res.     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-09-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8000036     Medline TA:  Arch Pharm Res     Country:  Korea (South)    
Other Details:
Languages:  eng     Pagination:  1363-72     Citation Subset:  IM    
Laboratory of Clinical Biology and Pharmacogenomics and Center for Clinical Research and Genomics, Kyung Hee University, Seoul, 130-701, Korea.
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