title: A natural musaceas plant extract inhibits proteasome activity and induces apoptosis selectively in human tumor and transformed, but not normal and non-transformed, cells.
abstract: Animal studies have demonstrated that a dietary polyphenol known as tannic acid (TA) exhibits anticarcinogenic activity in chemically induced cancers. Most recently, we have reported that TA and ester-bond containing green tea polyphenols are potent proteasome inhibitors in vitro and in vivo. We hypothesize that CellQuest, a patented formula which contains high level of TA obtained from a musaceas (plantain) plant extract, will inhibit the tumor cell proteasome activity. Here, we report that a partially purified CellQuest fraction, S3, potently inhibits the proteasomal chymotrypsin-like activity of Jurkat T cell extracts in a concentration-dependent manner. Inhibition of the proteasome by S3 in leukemia Jurkat T, simian virus 40-transformed and prostate cancer LNCaP cells results in accumulation of ubiquitinated proteins and the natural proteasome substrate p27Kip1, followed by induction of apoptosis. In contrast, non-transformed, immortalized human natural killer cells and normal human fibroblasts are resistant to S3-mediated proteasome inhibition and apoptosis induction. Our present study suggests that CellQuest targets and inhibits the proteasome selectively in tumor cells, which may contribute to the claimed anticancer activity.
authors: Drug Discovery Program, H. Lee Moffitt Cancer Center and Research Institute, University of South Florida, 12902 Magnolia Drive, Tampa, FL 33612, USA.
authors: Aslamuzzaman
authors: A
authors: Kazi
authors: Daniel A
authors: DA
authors: Urbizu
authors: Deborah J
authors: DJ
authors: Kuhn
authors: Abelardo L
authors: AL
authors: Acebo
authors: Edward R
authors: ER
authors: Jackson
authors: Gail P
authors: GP
authors: Greenfelder
authors: Nagi B
authors: NB
authors: Kumar
authors: Q Ping
authors: QP
authors: Dou
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002461:Cell Line, Transformed; D003546:Cysteine Endopeptidases; D006801:Humans; D019169:Jurkat Cells; D008297:Male; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors*; D028522:Musaceae / Q000378:metabolism*; D010936:Plant Extracts / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D046988:Proteasome Endopeptidase Complex
chemical_list: D009097:Multienzyme Complexes; D010936:Plant Extracts; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex