Purified Cucurbitacin D leads to alterations of apoptotic and autophagic genes expression in MDA-MB-468 and MCF-7 human breast cancer cells

Breast cancer is the second most frequent malignancy worldwide. The use of plant-derived drugs in cancer therapy are widely considered in the treatment of different malignancies including breast cancer. Cucurbitacin D (Cu D) is able to induce apoptosis in cancerous cells through different signaling pathways. The aim of this study was to examine the effect of different concentrations of Cucurbitacin D on viability, death pattern as well as the expression alterations of Bcl-2 , Bax , caspase-3 , p53, Atg5 , Beclin-1 , PTEN and Akt genes in the MCF-7 (ER positive) and MDA-MB-468 (triple negative) breast cancer cell lines. Two breast cancer cell lines (MCF-7 and MDA-MB-468) were cultured and treated with different concentrations of the purified Cucurbitacin D. Anti-proliferative effects of the Cucurbitacin D on both breast cancer cell lines viability was investigated using the MTT assay. Real-time PCR was applied to evaluate the expression levels of the genes upon Cucurbitacin D therapy. Significant dose-dependent and anti-proliferative effects of the Cucurbitacin D were observed on MCF-7 and MDA-MB-468 cells after 24 h with IC50 value about 30 and 25 µM, respectively (P < 0.01). Significant changes in expression of the genes in the breast cancer lines (MCF-7 and MDA-MB-468), were observed under different concentrations of Cucurbitacin D. Our results confirmed that the Cucurbitacin D may influence breast cancer cell lines viability at specific doses and by altering the expression of these genes. The differences between the gene’s aberrations in our breast cancer cell lines propose that these genes can have a distinct role in the pathophysiology and therapy responsiveness of various subtypes of breast cancer.