Inhibition of proteasome activity by various fruits and vegetables is associated with cancer cell death.
There is a large amount of scientific evidence showing that fruits and vegetables lower the risk of cancer. However, the responsible molecular mechanisms remain poorly understood. Our previous studies have demonstrated that inhibition of proteasomal chymotrypsin-like activity is associated with cancer cell apoptosis, which may also be the major mechanism responsible for the anticancer effects of green tea polyphenols. In the current study, we tested the hypothesis that some fruits and vegetables inhibit tumor cell proteasome activity and that this inhibition contributes to their cancer-preventative activities. We report that the extracts of apple and grape are more potent than onion, tomato and celery in: (i) inhibiting the proteasomal chymotrypsin-like activity in leukemia Jurkat T cell extract; (ii) accumulating the polyubiquitinated proteins in intact Jurkat T cells; (iii) inducing activation of caspase-3/-7 and cleavage of poly(ADP-ribose) polymerase in intact Jurkat T cells; and (iv) inducing the appearance of spherical cells preferentially in prostate cancer PC-3 over the normal NIH 3T3 cell line. We also found that strawberry extract had some effect on Jurkat T cell extract and the prostate PC-3 cell line but not on intact Jurkat T cells. Our findings suggest that the proteasome is a cancer-related molecular target for, at least, the extracts of apple, grape and onion, and that the inhibition of proteasome activity by these fruits or vegetable may contribute to their cancer-preventative effects, although other molecular mechanisms may also be involved.
Chen
Marina S
MS
The Prevention Program, Barbara Ann Karmanos Cancer Institute and Department of Pathology, Wayne State University, School of Medicine, Detroit, Michigan 48201, USA.
Chen
Di
D
Dou
Q Ping
QP
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002918:Chymotrypsin / Q000037:antagonists & inhibitors / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D005638:Fruit / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D051379:Mice; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D041681:NIH 3T3 Cells; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex; D013662:Tea; D014675:Vegetables / Q000737:chemistry / Q000502:physiology*
D000970:Antineoplastic Agents; D015853:Cysteine Proteinase Inhibitors; D009097:Multienzyme Complexes; D010936:Plant Extracts; D013662:Tea; D002918:Chymotrypsin; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex