Carcinogenesis Advance Access originally published online on May 23, 2007
Carcinogenesis 2007 28(10):2227-2235; doi:10.1093/carcin/bgm117
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Anthocyanin fraction from potato extracts is cytotoxic to prostate cancer cells through activation of caspase-dependent and caspase-independent pathways
Department of Horticultural Sciences
1 Center for Obesity Research and Program Evaluation, Nutrition and Food Science
2 Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX 77843, USA
3 Institute for Biosciences and Technology, Houston, TX 77030, USA
* To whom correspondence should be addressed. Tel: +1 979 847 8714; Fax: +1 979 862 1862; Email: jcmillerjr{at}tamu.edu
Correspondence may also be addressed to J.Creighton Miller Jr. Tel: +1 979 845 5488; Fax: +1 979 862 4929; Email: ssafe{at}cvm.tamu.edu
Polyphenols from fruits and vegetables exhibit anticancer properties both in vitro and in vivo and specialty potatoes are an excellent source of dietary polyphenols, including phenolic acids and anthocyanins. This study investigated the effects of specialty potato phenolics and their fractions on LNCaP (androgen dependent) and PC-3 (androgen independent) prostate cancer cells. Phenolic extracts from four specialty potato cultivars CO112F2-2, PATX99P32-2, ATTX98462-3 and ATTX98491-3 and organic acid, phenolic acid and anthocyanin fractions (AF) were used in this study. CO112F2-2 cultivar extracts and their AF at 5 µg chlorogenic acid eq/ml were more active and inhibited cell proliferation and increased the cyclin-dependent kinase inhibitor p27 levels in both LNCaP and PC-3 cells. Potato extract and AF induced apoptosis in both the cells and, however, the effects were cell context dependent. Cell death pathways induced by potato extract and AF were associated with mitogen-activated protein kinase and c-jun N-terminal kinase activation and these kinases activated caspase-independent apoptosis through nuclear translocation of endonuclease G (Endo G) and apoptosis-inducing factor in both cell lines. Induction of caspase-dependent apoptosis was also kinase dependent but was observed only in LNCaP cells. Kinase inhibitors reversed this nuclear translocation of endonuclease G and apoptosis-inducing factor. This is the first report showing that the cytotoxic activities of potato extract/AF in cancer cells were due to activation of caspase-independent apoptosis. Current studies are focused on identifying individual components of the AF responsible for the induction of cell death pathways in prostate and other cancer cell lines and developing potato cultivars that overexpress these active compounds.
Abbreviations: AF, anthocyanin fraction; AIF, apoptosis-inducing factor; AR, androgen receptor; DMSO, dimethyl sulfoxide; DPPH, 2,2-diphenyl-1-picrylhydrazyl radical; Endo G, endonuclease G; JNK, c-jun N-terminal kinase; MAPK, mitogen-activated protein kinase; NAC, N-acetyl cysteine; PF, phenolic acid fraction; TUNEL, terminal deoxynucleotidyl transferase mediated dutp nick end labeling; WST, water-soluble tetrazolium
Received December 22, 2006; revised May 10, 2007; accepted May 12, 2007.