| Abstract
Objective: Breast cancer is one of the most significant causes of female cancer death worldwide. Although several
chemotherapeutics have been developed to treat this type of cancer, issues remain such as low survival rates and high
reoccurrence after chemotherapy and radiotherapy. To explore a chemopreventive approach to enhancing breast cancer
treatment efficacy, the antiproliferative effects of a combination of chrysin and silibinin, two herbal substances, in T47D
breast cancer cells were assessed. Materials and Methods: Cytotoxicity of the agents singly and in combination was
evaluated by MTT assay. Also, qRT-PCR was used to measure the expression levels of hTERT and cyclin D1 genes after
48 h treatment. Results: Cell viability assays revealed that chrysin or silibinin alone inhibited proliferation in a dose
and time-dependent manner, and combining the drugs synergistically induced growth inhibition in the breast cancer cell
line. The precise nature of this interaction was further analyzed by the median-effect method, where the combination
indices (CI) were <1 for combination treatments, indicating synergism regarding T47D cell proliferation. qPCR results
showed that the drug combination also synergistically down-regulated the mRNA levels of hTERT and cyclin D1 at all
used concentrations compared with the drugs used alone after 48 h treatment (P ≤ 0.05). Conclusion: The data provide
evidence that synergistic antiproliferative effects of Chrysin and Silibinin are linked to the down-regulation of cyclin
D1 and hTERT genes, and suggest that their combination may have therapeutic value in treatment of breast cancer. |