Quercetin is a phytoestrogen flavonol found in a variety of fruits and vegetables. Studies regarding the influence of quercetin on breast cancer and breast cancer treatment have been numerous, and for the most part favorable. Women with high intakes of flavonols such as quercetin were found to have a 12% lower risk of breast cancer than those with low intakes in one study. Quercetin has been shown to inhibit insulin receptor signaling, which in turn reduces cancer cell proliferation. Quercetin can induce breast cancer cell death and has been reported to enhance the treatment effects of radiotherapy and chemotherapy. Quercetin has also been shown to protect heart cells from the toxic effects of Adriamycin (doxorubicin) chemotherapy.
However, a few studies have reported adverse effects of quercetin in some circumstances. For example, one study reported that quercetin contributed to the growth of estrogen-induced mammary tumors, but only once the tumors were established in female rats. In other words, supplemental quercetin did not prevent (or induce) tumor initiation but did contribute to tumor growth. Another study reported that while quercetin reduced the growth of glioma cells in the laboratory, it increased the volume of the brain tumors when administered to rats with gliomas. Gliomas are tumors arising from the supportive tissue of the brain. Now a new study presented at the annual AACR (American Association for Cancer Research) meeting in April has reported that while quercetin appears to protect heart cells from the toxic effects of Adriamycin, it can also reduce Adriamycin's treatment effects in some breast cancer cells.
Best food sources of quercetin
There is some evidence that the impact of flavonoids on breast cancer cells depends on the dosage, with low or high doses potentially stimulating breast cancer cell growth in some cases. When flavonoids are consumed as part of food, they are combined with other micronutrients that have been shown to act synergistically against breast cancer. Consuming flavonoid-rich foods is safe. On the other hand, safe and effective dosages of flavonoid supplements have not been established and such supplementation has the potential to increase breast cancer risk and reduce the effectiveness of treatment. Based on the available evidence, we conclude that quercetin should not be taken in supplement form.
Quercetin is abundant in the following foods:
Latest research finds quercetin can have dual role
The study referenced at the beginning of this news article was designed to investigate the actions of quercetin in breast cancer cells treated with Adriamycin. The authors first demonstrated that quercetin significantly protected an aorta model from Adriamycin-induced vascular toxicity. The ability of quercetin to protect the integrity of blood vessels may, in part, explain how it protects the heart. The authors then tested quercetin-Adriamycin combinations in ER+/PR+ (MCF-7 and T47D) and triple negative (MDA-MB-231) breast cancer cells.
Two drugs are considered synergistic if the combination is more effective than each drug used separately. On the other hand, two drugs are considered antagonistic if the combination is less effective, i.e., one of the drugs counteracts the actions of the other. One way to evaluate whether a combination is synergistic or antagonistic to calculate a combination index (CI) based on drug cytotoxicity curves.
Quercetin was found to double the IC50 (half maximal inhibitory concentration) of Adriamycin (from 0.4±0.03 to 0.8±0.06 μM) in MCF-7 cells and the CI value also indicated strong antagonism (i.e., reduction of its treatment efficacy). The IC50 of Adriamycin was not altered by quercetin in triple negative breast cancer cells, however the CI was indicative of antagonism. On the other hand, the quercetin-Adriamycin combination was synergistic in T47D cells, with an improved IC50 (reduced from 0.74±0.05 to 0.36±0.003 μM) and more favorable CI value.
Most solid tumors contain hypoxic regions with low oxygen conditions due to inadequate blood supply. Under hypoxic conditions, quercetin was found to synergize Adriamycin's cytotoxicity against MCF7 cells, significantly reducing its IC50. Additional experiments demonstrated that the combination of quercetin with Adriamycin significantly increased the concentration of pro-caspase 3 (which is involved in programmed cell death) compared to Adriamycin alone in T47D and triple negative cells. The authors conclude that, while quercetin protects vascular tissue from Adriamycin, it also has antagonistic to borderline synergistic interactions with Adriamycin in three different breast cancer cell lines.
Please see our article on what to eat while on Adriamycin for more information.