Dietary quercetin combining intratumoral doxorubicin injection synergistically induces rejection of established breast cancer in mice

Abstract

Dietary ingredients can decrease the risk of a variety of human cancers. Quercetin (3,3′,4′,5,7-pentahydroxyflavone) has a long history of consumption as part of the normal human diet and is able to induce growth inhibition in multiple cancer cells. In an attempt to generate more potent therapeutic effect for breast cancer, we have designed a combinative regimen of dietary quercetin with intratumoral doxorubicin injection and evaluated their anti-tumor activity in established breast cancer mouse model. Interestingly, dietary quercetin combining intratumoral doxorubicin injection synergistically induced potent rejection of 4T1 breast cancer and led to long-term, tumor-free survival in mice bearing established breast tumor, whereas quercetin or doxorubicin alone failed to cure tumor-bearing mice. Treatment with quercetin promoted lymphocyte proliferation and regulated Th1/Th2 cytokine imbalance. Combination of quercetin and intratumoral doxorubicin injection further induced a persistent T-cell tumor-specific responses. Based on these results, the combination of quercetin as a food supplement adjunctive with intratumoral doxorubicin chemotherapy may represent a novel and highly effective strategy for inducing immune responses against tumors.