Quercetin enhances chemotherapeutic effect of doxorubicin against human breast cancer cells while reducing toxic side effects of it

Doxorubicin (Dox) is an efficient drug for breast cancer chemotherapy, however, its toxic side effects on non-tumor tissues, especially on myocardial cells, sometimes limit its clinical application. Therefore, it is necessary to develop a new drug, which can be combined with Dox to potentiate the anti-tumor effect of Dox at a lower concentration and attenuate the toxic side effects of it. Quercetin (Que) has anti-tumor activity in addition to its protective effects on various cells. By preparing human non-tumoral MCF-10A mammary cells, human breast cancer MCF-7 and MDA-MB-231 cells and human myocardial AC16 cells, here, we wanted to evaluate whether Que might represent such an agent and investigate its possible mechanisms of potentiating the anti-tumor effect of Dox at a lower concentration. The results showed that Que could increase intracellular accumulation of Dox in breast cancer cells through down-regulating the expression of efflux ABC transporters including P-gp, BCRP and MRP1, which can effectively eliminate cancerous cells including breast cancer stem cells (BCSCs), thereby potentiating the anti-tumor effect of Dox. Furthermore, Que attenuated the cytotoxicity of Dox to non-tumoral MCF-10A mammary cells and myocardial AC16 cells. Therefore, Que could be used as a novel agent combined with Dox in breast cancer therapy, which could potentiate the anti-tumor effect of Dox at a lower concentration and attenuate the toxic side effects of it.