Abstract
Multidrug resistance (MDR) is a major obstacle to the chemotherapeutic treatment of breast cancer. Germacrone, the main component of Rhizoma Curcuma, has been shown to possess antitumor, anti-inflammatory and immunomodulatory properties. The aim of the present study was to investigate the effect of germacrone on MCF-7/Adriamycin (ADR) multidrug-resistant human breast cancer cells. The treatment of MCF-7/ADR cells with a combination of germacrone and ADR resulted in an increase in cytotoxicity compared with that of ADR alone, as determined using an MTT assay. Flow cytometric analysis revealed that germacrone promoted cell apoptosis in a dose-dependent manner, whilst treatment with germacrone plus ADR enhanced the apoptotic effect synergistically. Furthermore, the results from the western blot analysis demonstrated that augmenting ADR treatment with germacrone resulted in a reduction of anti-apoptotic protein expression levels (bcl-2) and enhancement of pro-apoptotic protein expression levels (p53 and bax) in MCF-7/ADR cells compared with the levels achieved by treatment with ADR alone. In addition, germacrone significantly reduced the expression of P-glycoprotein via the inhibition of the multidrug resistance 1 (MDR1) gene promoter. These findings demonstrate that germacrone has a critical role against MDR and may be a novel MDR reversal agent for breast cancer chemotherapy.
Highlights
Breast cancer has emerged as the most common malignancy observed in females worldwide
The results showed that the IC50 of ADR at 48 h was 1.27±0.12 μmol/l in MCF‐7 cells and 87.40±5.24 μmol/l in MCF‐7/ADR cells (Fig. 1A and B)
Treatment with a combination of germacrone and ADR inhibited cell viability synergistically (Fig. 1D). These results demonstrate that the treatment of MCF‐7/ADR cells with a combination of germacrone and ADR results in an increase in cytotoxicity
Summary
Breast cancer has emerged as the most common malignancy observed in females worldwide. It is the leading cause of cancer mortalities among females, accounting for 23% of total cancer cases and 14% of cancer mortalities [1]. Chemotherapy is one of the main treatments for patients diagnosed with breast cancer. Resistance to chemotherapeutic drugs has gradually emerged [2]. Resistance to chemotherapeutics, in particular, multidrug resistance (MDR), remains the leading cause of chemotherapy failure. The MDR mechanism is an extremely complicated process, involving drug metabolic biotransformation, drug efflux increase and alteration of the repair ability for anticancer drug‐induced DNA damage [3,4]. It is imperative to find novel and effective strategies to reverse drug resistance
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