Structure-proteasome-inhibitory activity relationships of dietary flavonoids in human cancer cells.
Diet high in vegetables and fruits has been associated with reduced cancer risk. However, the involved mechanisms are unknown. Previously, we reported that the dietary flavonoid apigenin could inhibit the proteasome activity and induce apoptosis in tumor cells. To further investigate the structure-proteasome-inhibitory activity relationships, we chose and tested five dietary flavonoids, including luteolin, apigenin, chrysin, naringenin and eriodictyol. We found that the order of inhibitory potencies and apoptosis-inducing potencies of these five compounds in 20S purified proteasome and tumor cells was: (1) luteolin > apigenin > chrysin, and (2) apigenin >> naringenin, and luteolin >> eriodictyol. Therefore, flavonoids with hydroxylized B ring and/or unsaturated C ring are natural potent proteasome inhibitors and tumor cell apoptosis inducers. Furthermore, neither apigenin nor luteolin could inhibit the proteasome and induce apoptosis in non-transformed human natural killer cells. This finding may provide a molecular basis for the clinically observed cancer-preventive effects of fruits and vegetables.
Chen
Di
D
The Prevention Program, Barbara Ann Karmanos Cancer Institute, and Department of Pathology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Chen
Marina S
MS
Cui
Qiuzhi Cindy
QC
Yang
Huanjie
H
Dou
Q Ping
QP
D016588:Anticarcinogenic Agents / Q000737:chemistry* / Q000494:pharmacology*; D047310:Apigenin / Q000494:pharmacology; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D004032:Diet; D005419:Flavonoids / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D019169:Jurkat Cells; D007694:Killer Cells, Natural / Q000201:enzymology; D047311:Luteolin / Q000494:pharmacology; D008297:Male; D011471:Prostatic Neoplasms / Q000201:enzymology; D011480:Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology; D061988:Proteasome Inhibitors; D013329:Structure-Activity Relationship
D016588:Anticarcinogenic Agents; D005419:Flavonoids; D011480:Protease Inhibitors; D061988:Proteasome Inhibitors; D047310:Apigenin; D053148:Caspase 3; D047311:Luteolin