Quercetin is a phytoestrogen flavonol found in a variety of fruits and vegetables. Population studies have consistently found that high-flavonol diets are associated with reduced breast cancer risk. For example, women with high intakes of flavonols were found to have a 12% lower risk of breast cancer than those with low intakes in one study. Most foods with significant quercetin content have been found to be associated with reduced breast cancer risk.

Quercetin has been shown to induce the death of hormone receptor positive (ER+/PR+), HER2 overexpressing (HER2+) and triple negative (ER-/PR-/HER2-) breast cancer cells while not harming normal breast cells. Quercetin inhibits insulin receptor signaling, which in turn reduces cancer cell proliferation. Quercetin has also been found to inhibit angiogenesis (the growth of new blood vessels) of mammary tumors in a mouse model of breast cancer. In addition, quercetin has been reported to enhance the treatment effects of radiotherapy and chemotherapy. Quercetin also appears to protect heart cells from the toxic effects of Adriamycin (doxorubicin) chemotherapy. Now a new study has reported that that quercetin can inhibit the recruitment of regulatory T cells by triple negative breast cancer cells, thereby reducing tumor growth.

Best food sources of quercetin

Quercetin is abundant in the following foods:

Black tea
Cranberries & lingonberries
Currants, black
Dill, fresh

Green onions or scallions
Green tea
Hot peppers
Onions, red

Quercetin supplements should be avoided

The impact of flavonoids such as quercetin 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 can act synergistically with them against breast cancer. Consuming flavonoid-rich foods is safe and could help prevent breast cancer or its recurrence. On the other hand, safe and effective dosages of flavonoid supplements have not been established and they have the potential to increase breast cancer risk or reduce the effectiveness of treatment.

A number of studies have reported that quercetin can kill breast cancer cells and even enhance the treatment effects of radiation treatment and chemotherapy. However, several studies have reported that quercetin can promote cancer. 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 induce tumor initiation but did contribute to tumor growth. Another study reported that quercetin could promote multi-drug resistance in tumor cells and reduce the efficacy of chemotherapy under some circumstances. Based on the available evidence, we conclude that quercetin should not be taken in supplement form.

Latest research finds quercetin can inhibit TN tumor growth

The study referenced at the beginning of this news story was designed to investigate the effects of quercetin in MDA-MB-468 triple negative breast cancer cells. Breast tumors are known to recruit regulatory T cells (Tregs). Tregs normally are an important element of the immune system. However, they can be subverted by nearby breast cancer cells to promote hypoxia-driven angiogenesis. Tumor hypoxia is a low-oxygen condition under which solid breast tumors can still thrive.

In the study, the authors examined the effects of quercetin on the release of tumor necrosis factor-alpha (TNF-α)-induced tumor promoting chemokines (a type of chemical that has the ability to attract white blood cells to sites of infection) in triple negative cells, with a focus on those associated with Tregs recruitment. TNF-α, which is involved in systemic inflammation, has previously been shown to promote tumor cell growth in a dose-dependent manner. Tumor hypoxia in other cancer types has been shown to promote the recruitment of Tregs through induction of the expression of the chemokine CC-chemokine ligand 28 (CCL28), which in turn promotes both tolerance of the tumor by the immune system and angiogenesis to provide a blood supply for the tumor.

The authors first used antibody microarrays to establish that TNF-α-induced expression of various relevant proteins, including CCL28, were downregulated by a sublethal concentration of quercetin. The authors then demonstrated that quercetin downregulated TNF-α-induced CCL28 release by 60%. Little has been known regarding the presence of CCL28 in breast cancer until now. The authors conclude that the findings suggest that quercetin can affect CCL28 release, thereby inhibiting the recruitment of Tregs, which is known to be an important factor in tumor cell growth.

Please see our article on triple negative diet for more information.