Pinocembrin triggers Bax-dependent mitochondrial apoptosis in colon cancer cells

✍ Scribed by M. A. Suresh Kumar; Mangalam Nair; P.S. Hema; John Mohan; T.R. Santhoshkumar

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 385 KB
• Volume: 46
• Category: Article
• ISSN: 0899-1987
• DOI: 10.1002/mc.20272

✦ Synopsis

Abstract

Bioflavanoids are the major pigments in plants with multitude of biological activities including inhibition of proliferation or induction of apoptosis in tumor cells. Eventhough the safety records of most flavanoids are exceptional, its therapeutic use is still in its infancy. We have isolated pinocembrin (5,7‐dihydroxyflavanone) from Alpinia galanga that showed cytotoxicity against a variety of cancer cells including normal lung fibroblasts with relative nontoxicity to human umbilical cord endothelial cells. The compound induced loss of mitochondrial membrane potential with subsequent release of cytochrome c and processing of caspase‐9 and ‐3 in colon cancer cell line HCT 116. Processing of caspase‐8 was minimal. The initial trigger for mitochondrial apoptosis appears to be by the translocation of cytosolic Bax protein to mitochondria. Overexpression of proapoptotic Bax protein sensitized the colon cancer cells to pinocembrin‐induced apoptosis and Bax knockout cells were resistant to pinocembrin‐induced apoptosis. Antiapoptotic protein Bcl‐X~L~ only partially prevented apoptosis induced by this compound. The Bax‐dependent cell death involving classical cytochrome c release and processing of caspase‐9 and ‐3 suggests that pinocembrin is a classical mitochondrial apoptosis inducer. But the failure of Bcl‐X~L~ overexpression to completely prevent apoptosis induced by this compound suggests that pinocembrin is capable of triggering mitochondrial‐independent cell death that needs to be clarified. The existence of cell death upon Bcl‐X~L~ overexpression is a promising feature of this compound that can be exploited against drug resistant forms of cancer cells either alone or in combination with other drugs. © 2006 Wiley‐Liss, Inc.