An Investigation of Anticancer Effects of Doxorubicin and Calcitriol Combination on MCF-7 Cells

Abstract

<strong>Objectives</strong>: This study aimed to identify a substance that both increases the efficiency and decreases the dose of doxorubicin. Doxorubicin has considerable cardiac side effects at certain doses when used treating breast cancer. Calcitriol, one of the vitamin D analogs considered to have antiproliferative effects, was selected, and its cytotoxic effects on the human breast cancer cell line MCF7 were investigated in combination with doxorubicin. <br> <strong>Materials and Methods</strong>: MCF-7 cell line was treated with calcitriol in real time for 72 h in x-CELLigence. The antiproliferative optimal dose of calcitriol was determined by time-dependent cell index graph plotted using The xCELLigence Real-Time Cell Analysis (RTCA) software program. The combination of different doses of doxorubicin and this optimal dose of calcitriol was used to treat the MCF-7 cell line. Then, Sulforhodamine-B (SRB) assay was conducted, and spectrophotometric measurements were performed for cytotoxicity assay. The results of these spectrophotometric measurements were analyzed by Student’s -test. <br> <strong>Results</strong>: The optimal antiproliferative calcitriol dose detection of MCF-7 cells was performed using the time-dependent cell index graph RTCA software program. Spectrophotometric measurements obtained using the protein-staining sulforodamine B (SRB) assay for cytotoxicity determination were statistically evaluated by the Student’s t-test using the GraphPad Prism program. The optimal dose of calcitriol was determined to be 250 nM. Different doses of doxorubicin (1.84-0.92 µM), calcitriol (250 nM), and calcitriol without the MCF-7 cell line were then used for detecting the cytotoxic effect. The combination of 0.46 µM doxorubicin and the optimal dose of calcitriol was found to be cytotoxic compared with other doses (p=0.0087); however, it was not as effective as the dose reduction obtained when using doxorubicin. <br> <strong>Conclusion</strong>: The combined use of doxorubicin with calcitriol was found to have no significant effect in reducing the doses presently being used. Hence, it is too early to state that a combination of vitamin D and doxorubicin in breast cancer treatment will not have any beneficial effects. Other vitamin D analogs might be potential candidates for breast cancer treatment in further studies.