Breast cancer is a malignant disease with an increasing incidence. Chemotherapy is still an important means for breast cancer treatment, but multidrug resistance (MDR) greatly limits its clinical application. Therefore, the high-efficiency MDR reversal agents are urgently needed. Traditional Chinese medicine (TCM) monomers have unique advantages in reversing chemotherapeutic MDR because of its low toxicity, high efficiency, and ability to impact multiple targets. This review firstly summarizes the major mechanisms of MDR in breast cancer, including the reduced accumulation of intracellular chemotherapeutic drugs, the promoted inactivation of intracellular chemotherapeutic drugs, and the enhanced damage repair ability of DNA, etc., and secondly highlights the research progress of 15 kinds of TCM monomers, including curcumin, resveratrol, emodin, apigenin, tetrandrine, gambogic acid, matrine, paeonol, schisandrin B, [Formula: see text]-elemene, astragaloside IV, berberine, puerarin, tanshinone IIA, and quercetin, in reversing MDR of breast cancer. This review also provides the suggestion for the future research of MDR reversal agents in breast cancer.

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Objective. Local radiotherapy may cause distant tumor regression via inducing immunogenic cell death (ICD). Here, we investigated the effect of curcumin on ionizing radiation-induced immunogenic cell death in normoxic or hypoxic glioma cells and its mechanism in vitro and vivo. Methods. Hypoxic or normoxic glioma cell apoptosis and the cell surface exposure of calreticulin (CRT) were detected by flow cytometry. Extracellular ATP and HSP70 were measured by chemiluminescence assay and ELISA, respectively. Endoplasmic reticulum (ER) stress protein levels were detected by western blot. Moreover, the induction of bona fide ICD was detected by vaccination assays in mice bearing glioma model. Spleen lymphocytes and tumor-infiltrating lymphocyte subsets were analyzed by flow cytometry and immunohistochemistry. Results. Curcumin incubation before X-ray irradiation significantly increased radiation-induced apoptosis rate in normoxic or hypoxic glioma cells. Curcumin enhanced radiation-induced CRT exposure, release of HSP70 and ATP, and ER stress signaling activity. After treatment with ER stress pathway inhibitors, cell apoptosis and CRT exposure induced by the combination treatment of curcumin and X-ray were reduced. In vaccination experiments, glioma cells irradiated by X-ray produced a strong immunogenic response rejecting tumor formation in 70% mice. In comparison, cells treated by curcumin and X-ray produced a stronger immune response rejecting tumor formation in 90% mice. The combination treatment increased the percentage of tumor-infiltrating CD4+, CD8+ T lymphocytes, and CD11c+ dendritic cells compared to X-ray irradiation alone. Conclusion. Ionizing radiation-induced normoxic or hypoxic glioma immunogenic cell death could be further enhanced by curcumin through activating the ER stress PERK-eIF2α and IRE1α-XBP1 signaling pathways.

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