Abstract：
:25-Hydroxy-3-oxoolean-12-en-28-oic acid (Amooranin-AMR) is a triterpene acid isolated from the stem bark of a tropical tree (Amoora rohituka) grown wild in India. A herbal preparation used for the treatment of cancer by the Ayurvedic system of medicine contains the stem bark of Amoora rohituka as one of the ingredients. In this paper, we show that AMR displays a strong inhibitory effect on survival of human breast carcinoma MDA-468, breast adenocarcinoma MCF-7 cells compared to breast epithelial MCF-10A control cells. A 50% decrease in cells (IC50) ranged from 1.8 to 14.6 microM and cell growth was suppressed by arresting cell cycle at G2 + M phase. AMR effectively induces apoptosis and triggered a series of effects associated with apoptosis including cleavage of caspase-8, -9, -3, Bid and ER stress in MDA-468 cells and caspase- 8, -9, -6 and Bid in MCF-7 cells, release of cytochrome c from the mitochondria, cleavage of poly (ADP-ribose) polymerase (PARP) and DNA fragmentation with a concomitant upregulation of p53, Bax and down-regulation of Bcl-2 in MDA-468 cells, but Bax unchanged in MCF-7 cells. The use of caspase blocking peptides and acridine orange staining confirmed the involvement of primarily caspase-9 and -3 in MDA-468 cells with mutated p53 and primarily caspase-8, -9 and -6 in MCF-7 cells expressing wt p53. We also observed in MCF-7/p53siRNA cells AMR treatment caused reduced expression of Bcl-2 without affecting levels of Bax similar to MCF-7 cells treated with AMR and proteolytic activation of Bax in MDA-468 cells. These results suggest that AMR induces apoptosis in human breast carcinoma cells via caspase activation pathway and likely it is a p53-independent apoptosis.
journal_name
Breast Cancer Res Treatjournal_title
Breast cancer research and treatmentauthors
Rabi T,Wang L,Banerjee Sdoi
10.1007/s10549-006-9275-zsubject
Has Abstractpub_date
2007-01-01 00:00:00pages
27-36issue
1eissn
0167-6806issn
1573-7217journal_volume
101pub_type
杂志文章abstract：:The transcriptome of breast cancers have been extensively screened with microarrays and large sets of genes associated with clinical features have been established. The aim of this study was to validate original gene sets on a large cohort of raw breast cancer microarray data with known clinical follow-up. We recovere...
journal_title：Breast cancer research and treatment
pub_type： 杂志文章,meta分析
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doi：10.1023/a:1005732531318
更新日期：1997-06-01 00:00:00
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journal_title：Breast cancer research and treatment
pub_type： 临床试验,杂志文章,随机对照试验
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更新日期：1997-09-01 00:00:00
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pub_type： 临床试验,杂志文章,随机对照试验
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更新日期：1997-02-01 00:00:00
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更新日期：2010-01-01 00:00:00
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pub_type： 临床试验,杂志文章
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更新日期：1996-01-01 00:00:00
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