Curcumin boosts doxorubicin cytotoxicity in breast cancer cells

Background. Breast cancer remains the leading cause of cancer mortality in women due to the resistance to chemotherapy and severe side effects of doxorubicin (Doxo). One of the approaches to overcome this problem is to search for phytocompounds that can enhance the efficacy of chemotherapy and prevent the development of side effects. Objective. This work aimed to investigate in vitro whether the polyphenol curcumin (Cur) from turmeric (Curcuma longa) in combination with the commercial drug Doxo-HCl can enhance the cytotoxic effect of Doxo on breast cancer cell lines MDA-MB-231 and MCF-7 and to exhibit chemoprotective activity against normal HEK-293 cells. Methods. Cell viability was assessed with MTT assay, apoptosis induction by flow cytometry with Annexin V–eGFP and PI, reactive oxygen species (ROS) generation by the DCFH-DA probe. The combination index (CI) calculation method and CompuSyn, Biosoft software were used to determine the synergism or antagonism of the components. Results. The study revealed dose-dependent cytotoxicity, increased ROS formation, and increased morphological aberrations in cells when using the combination of Cur with Doxo-HCl compared to Doxo-HCl. Cur acted as a chemosensitizer, which synergistically enhanced the antitumor activity of Doxo-HCl while simultaneously reducing its cytotoxic effects in normal cells by reducing ROS production. Conclusions. The use of Cur in combination with Doxo-HCl will likely reduce the effective therapeutic dose of Doxo and increase the effectiveness of breast cancer chemotherapy. Keywords: apoptosis, breast cancer cell lines, cell viability, chemosensitizer, combination index, combined treatment, curcumin, doxorubicin, oxidative stress