Annually about 10 million people develop cancer and about 6.2 million people die of cancer worldwide. Cancer cells have altered chemical pathways that lead to rapid growth and division of cells and reduced apoptosis (cell suicide). Overriding these functions can be therapeutic in patients with cancer and the proteasome pathway plays a role in these functions.
Proteasome activity is necessary for cancer cell survival. Proteasome is a very complex protease enzyme, with trypsin, chymotrypsin and caspase activity. The consumption of fruits and vegetables is known to reduce cancer risk. Various fruits and vegetable extracts, especially grape extracts, inhibit proteasome activity and induced cell apoptosis in tumor cells. The flavonoid epigallocatechin-3-gallate (EGCG) inhibits the proteasome in vivo (in life) and in vitro (in the lab) at the level found in the blood of tea drinkers.
The authors studied the flavonoids apigenin, quercetin, kaempferol and myricetin. All of these flavonoids are in grape juice except apigenin, which is in chamomile and celery seed. These flavonoids were studied for their proteasome inhibiting activity, their apoptosis inducing activity, and their ability to fight cancer. Cancer cells have abnormalities in the apoptosis signaling pathways that leads to a reduction in the frequency of cell death and increased tumor growth. If these abnormalities can be overcome, tumor cell death results.
All four of the above flavonoids were studied in vitro against leukemia cells for their ability to inhibit proteasome. The best inhibition was by apigenin, followed by quercetin, kaempferol and myricetin, in that order. Chrysin and luteolin are analogs of apigenin that have apoptosis effects similar to apigenin, according to preliminary studies. Apoptosis was not induced in normal cells as it was in tumor cells. Green tea polyphenols and the soy isoflavone, genistein, have similar apoptosis induction effects in abnormal cells.
CONCLUSION: The cancer-preventive effects of flavonoids may be due to the inhibition of proteasome enzymes. Apigenin and quercetin were the most potent at proteasome inhibition and apoptosis induction in human cancer cells. Apigenin did not inhibit the proteasome or induce apoptosis in normal human natural killer (NK) cells, which had not been transformed into cancer cells. The authors feel that their study confirms that flavonoids work to inhibit proteasome for cancer prevention. Proteosome inhibition may contribute to the cancer-prevention effects of apigenin and quercetin.
NOTE: Apoptosis is a chemically induced form of internal cell suicide for abnormal cells. It is a natural form of cell death, which is preferred because it results in little local inflammation. It is interesting that apoptosis was induced in this study only in cells which were abnormal. This increases the benefits of the use of flavonoids in cancer since normal cells do not seem to be harmed.
Proteasome is an enzyme that regulates protein production in cells, especially proteins that relate to the cell’s cycle and apoptosis. Preclinical studies have shown that proteasome inhibition can reduce cell proliferation, increase apoptosis and sensitize cancer cells to chemotherapy and irradiation.
Curcumin (turmeric extract), green tea and mate have been shown as having proteasome inhibitor activity in addition to the above products.
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