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.