Objective:

The aim of this study was to investigate the anti-cancer effects of arbutin on doxorubicin-induced cytotoxicity in the double-positive estrogen receptor +/ progesterone receptor +/ human epidermal growth factor receptor 2 negative (ER+/PR+/HER2-) breast cancer (BC) cell line MCF-7 in vitro.

Materials and Methods:

Viability screening was performed with colorimetric MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay. Intracellular reactive oxygen species (ROS) accumulation was evaluated by dihydrorhodamine 123 (DHR123) staining. Apoptosis, necrosis and viability to arbutin, doxorubicin and their combination were assessed by Annexin V/7-AAD (7-aminoactinomycin D) staining. Cell cycle phase distribution was analyzed by DNA content analysis.

Results:

Arbutin alone, at concentrations up to 500 µM, did not reduce MCF-7 cell viability over incubation periods ranging from 6 to 48 hours. Arbutin at concentrations above 20 µM transiently decreased intracellular ROS levels at 6 hours but had no significant effect at 24 and 48 hours. When combined with doxorubicin, arbutin partially reversed doxorubicin-induced reductions in cell viability, decreased late apoptosis and necrosis rates, and regulated doxorubicin-induced cell cycle disruptions.

Conclusions:

These results suggest that while arbutin does not exhibit direct cytotoxicity in MCF-7 cells, it modulates doxorubicin-induced cellular responses. Future studies with arbutin at higher concentrations investigating the molecular mechanisms underlying this effect, particularly at the gene and protein expression levels, are necessary to further elucidate the potential role of arbutin in BC therapy.

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