Abstract
Chemotherapy plays a key role in breast cancer therapy, but drug resistance and unwanted side effects make the treatment less effective. We propose a new combination model that combines antineoplastic drugs and antimalarials for breast cancer therapy. Cytotoxic effects of two antineoplastic agents alone and in combination with several antimalarials on MCF-7 tumor cell line was evaluated. Different concentrations in a fixed ratio were added to the cultured cells and incubated for 48 h. Cell viability was evaluated using MTT and SRB assays. Synergism was evaluated using the Chou-Talalay method. The results indicate doxorubicin (DOX) and paclitaxel (PTX) alone at concentrations of their IC50 and higher are cell growth inhibitors. Mefloquine, artesunate, and chloroquine at concentrations of their IC50 demonstrate anti-cancer activity. In combination, almost all antimalarials demonstrate higher ability than DOX and PTX alone to decrease cell viability at concentrations of IC50 and lower than their IC50. The combination of chloroquine, artesunate and mefloquine with DOX and PTX was synergic (CI < 1). The combination of DOX and mefloquine after 48 h incubation demonstrated the highest cytotoxicity against MCF-7 cells, and the combination of DOX and artesunate was the most synergic. These results suggest antimalarials could act synergistically with DOX/PTX for breast cancer therapy.
Highlights
Breast cancer is the most commonly diagnosed type of cancer in women and represents the second leading cause of death by cancer in women worldwide [1]
Human breast cancer MCF-7 cell line was obtained from the American Type Culture Collection (ATCC; Virginia, USA) and maintained according to ATCC’s recommendations at 37 ◦C and 5% CO2 in DMEM medium supplemented with 10% fetal bovine serum, 100 U/mL penicillin G, and 100 μg/mL streptomycin
Our results demonstrated that antimalarial drugs as single agents have ability to decrease cell viability in a concentration-dependent manner and in combination can improve the anti-cancer activity of DOX and PTX in ER-positive breast cancer cells
Summary
Breast cancer is the most commonly diagnosed type of cancer in women and represents the second leading cause of death by cancer in women worldwide [1]. More than 30 clinical studies are currently evaluating the activity of this antimalarial drug combined with various standard treatments in different types of cancer The idea behind this strategy is that chloroquine can increase tumor cells sensibilization and potentiate the therapeutic activity of chemotherapeutic drugs [44]. We demonstrate that the combination of DOX/PTX and some antimalarials such as artesunate, chloroquine, and mefloquine induces a greater anti-tumor effect compared to each drug alone in MCF-7 breast cancer cell line. These results should be confirmed in vivo and may be significant clinically. Mefloquine (cat. no. sc-211784) was purchased from Santa Cruz Biotechnology (Dallas, Texas, USA)
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