Bortezomib is a pharmaceutical proteasome inhibitor which is a strong treatment for multiple myeloma. Bortezomib induces apoptosis in leukemia cells in the laboratory. Yet, it is not effective in human studies of chronic lymphocytic leukemia (CLL). (Proteasome inhibition in the bone marrow is 1/2 that in the blood.)
We eat about 23 mg. of flavonoids each day. Quercitin is a flavonoid in fruits and vegetables (especially onions.) It is a strong antioxidant, blocks the proteasome to induce apoptosis and has antiaging and anticancer effects. Quercitin has been shown to block the apoptosis of leukemia cells initiated by bortezomib. Quercetin and bortezomib block proteasome activity in similar ways. The flavonoids myricetin, kaempferol, luteolin and apigenin act in ways similar to quercetin, although weaker.
The blocking effect of quercetin on apoptosis induced by bortezomib was studied in CLL and B-cell lines. In CLL, quercetin induced apoptosis at 20 micromols concentration. At the same time, quercetin blocked bortezomib-induced apoptosis at 20 micromols. Quercitin, at 40 micromols, completely inhibited the apoptosis of myeloma cell lines induced by bortezomib. At high doses, quercetin produced apoptosis of tumor cells.
The antioxidant N-acetyl cysteine (NAC) did not inhibit bortezomib-induced apoptosis in CLL cells in the laboratory. Boric acid inhibited the ability of quercetin to block bortezomib. A combination of boric acid and bortezomib is suggested as a good combination for treatment of human leukemia. (“..ingested inorganic boric acid is even safer than table salt.”)
CONCLUSION: This study indicates that quercetin inhibits apoptosis induced by the pharmaceutical bortezomib in B-cell leukemia and CLL. Dietary quercitin could be the reason bortezomib does not work for CLL. In multiple myeloma cells quercetin supported the activity of bortezomib. Patients on proteasome inhibitors should be given dietary information about the above interactions between bortezomib and flavonoids.
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