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Pinocembrin triggers Bax‐dependent mitochondrial apoptosis in colon cancer cells
Author(s) -
Kumar M. A. Suresh,
Nair Mangalam,
Hema P.S.,
Mohan John,
Santhoshkumar T.R.
Publication year - 2007
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.20272
Subject(s) - pinocembrin , apoptosis , cytochrome c , biology , mitochondrion , programmed cell death , microbiology and biotechnology , cancer cell , bcl 2 associated x protein , hela , caspase , intrinsic apoptosis , caspase 3 , biochemistry , cell , cancer , genetics , flavonoid , antioxidant
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.