Novel synthetic triterpenoid methyl 25-Hydroxy-3-Oxoolean-12-en-28-Oate induces apoptosis through JNK and p38 MAPK pathways in human breast adenocarcinoma MCF-7 cells

✍ Scribed by Thangaiyan Rabi; Sipra Banerjee

• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 354 KB
• Volume: 47
• Category: Article
• ISSN: 0899-1987
• DOI: 10.1002/mc.20399

✦ Synopsis

Abstract

Breast cancer is the most common neoplasm in women and is the leading cause of cancer‐related death for women. Therefore, new agents targeting prevention and treatment of breast cancer are urgently needed. The present study first investigates that a novel triterpenoid Methyl 25‐Hydroxy‐3‐oxoolean‐12‐en‐28‐oate (AMR‐Me) derived from 25‐Hydroxy‐3‐oxoolean‐12‐en‐28‐oic acid (AMR) is a potent inhibitor of cell growth by inducing human breast cancer MCF‐7 cells to undergo apoptosis. AMR‐Me induced DNA fragmentation and PARP degradation which were preceded by changing Bax/Bcl‐2 ratios, cytochrome c release, and subsequent induction of pro‐caspase‐9 and ‐7 processing in breast carcinoma MCF‐7 cells, but it did not act on Fas/Fas ligand pathways and the activation of caspase‐8, suggesting AMR‐Me triggered the mitochondrial apoptotic pathway. The general caspase blocking peptide VAD partially blocked AMR‐Me induced apoptosis. AMR‐Me stimulated p38 mitogen‐activated protein kinase and c‐Jun NH2‐terminal kinase (JNK), but not extracellular signal‐regulated kinase activation during apoptosis. SP600125, a specific inhibitor for JNK and SB203580, a p38 MAPK‐specific inhibitor suppressed AMR‐Me induced apoptosis indicating that activation of JNK and p38 MAPKs involved in the mitochondrial activation‐mediated cell death pathway. Our results suggest that AMR‐Me can utilize two different MAPK signaling pathways for amplifying the apoptosis cascade, is critical for both our understanding of cell death events and development of cancer preventive/therapeutic agents. © 2007 Wiley‐Liss, Inc.