Dietary flavonoids inhibit the anticancer effects of the proteasome inhibitor bortezomib.

Dietary flavonoids have many health-promoting actions, including anticancer activity via proteasome inhibition. Bor-tezomib is a dipeptide boronate proteasome inhibitor that has activity in the treatment of multiple myeloma but is not effective in chronic lymphocytic leukemia (CLL). Although CLL cells are sensitive in vitro to bortezomib-induced apoptosis when cultured in medium, the killing activity was blocked when cultured in 50% fresh autologous plasma. Dietary flavonoids, quercetin and myricetin, which are abundant in plasma, inhibited bortezomib-induced apoptosis of primary CLL and malignant B-cell lines in a dose-dependent manner. This inhibitory effect was associated with chemical reactions between quercetin and the boronic acid group, -RB(OH)2, in bortezomib. The addition of boric acid diminished the inhibitory effect of both quercetin and plasma on bortezomib-induced apoptosis. The protective effect was also reduced when myeloma cell lines, but not B-cell lines, were preincubated with quercetin, indicating a direct effect of quercetin on myeloma cells. At high doses, quercetin itself induced tumor cell death. These data indicate that dietary flavonoids limit the efficacy of bortezomib, whereas supplemental inorganic boric acid is able to reverse this. The complex interactions between quercetin, tumor cells, and bortezomib mean caution is required when giving dietary advice to patients.

Patients previously treated for lymphoma consume inadequate or excessive amounts of five key nutrients.

Adequate amounts of nutrients such as folate, vitamin A, iron, selenium and calcium are essential for general health including prevention of cancer. Yet, excess amounts of vitamin A, folate, and iron may also promote cancer. This study sought to determine whether adults who had completed initial treatments for B-cell lymphoma from 1 to 3 years earlier were consuming recommended amounts of these key nutrients and their interests in nutritional education. We surveyed 141 patients undergoing follow-up in the Lymphoma/Myeloma Clinic at The University of Texas M. D. Anderson Cancer Center using a validated food frequency questionnaire and supplemental questionnaire regarding nutritional interest. Nutrient intakes were estimated based on national databases of average content in foods and compared with recommended guidelines. One hundred forty-one participants returned complete questionnaires, but errors limited some nutrient estimates to 134 participants. Participants' mean age was 50, 55% were male, and 80% were non-Hispanic whites. Most participants (94%) were consuming either inadequate or excessive amounts of one or more of these key nutrients. Half of the participants were interested in receiving nutritional education. These findings are of concern because of their potential impact upon recovery and maintenance of general health and possibly cancer-related pathways after treatment.