A natural musaceas plant extract inhibits proteasome activity and induces apoptosis selectively in human tumor and transformed, but not normal and non-transformed, cells.
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.
Kazi
Aslamuzzaman
A
Drug Discovery Program, H. Lee Moffitt Cancer Center and Research Institute, University of South Florida, 12902 Magnolia Drive, Tampa, FL 33612, USA.
Urbizu
Daniel A
DA
Kuhn
Deborah J
DJ
Acebo
Abelardo L
AL
Jackson
Edward R
ER
Greenfelder
Gail P
GP
Kumar
Nagi B
NB
Dou
Q Ping
QP
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
D009097:Multienzyme Complexes; D010936:Plant Extracts; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex