Anticancer and anti-metastasis activity of 1,25 dihydroxycholecalciferols and genistein in MCF-7 and MDA-MB-231 breast cancer cell lines

Abstract

A powerful steroid hormone precursor, 1,25 dihydroxycholecalciferols (1,25(OH)₂D₃), and dietary phytoestrogen (genistein) are essential compounds that act by binding to nuclear receptors and altering gene expression. They have many biological benefits, some of which have anticancer properties. We studied the impact of 1,25(OH)₂D₃ and genistein on the proliferation, progression, and metastasis of MCF-7 and MDA-MB-231 cells when they were used alone or in combination and investigated whether there was a synergistic effect between genistein and 1,25(OH)₂D₃. To achieve these goals, a variety of assays, including flow cytometry, cell invasion assays, cell adhesion assays, Western blotting, and RT‒PCR, were used. Our findings showed that genistein, 1,25(OH)₂D₃, and the two combined all effectively declined the growth of MCF-7 and MDA-MB-231 cells by arresting the cells in the G0/G1 phase and inducing an apoptotic pathway. Stimulation of apoptosis was achieved by upregulating the expression of BAX and CASP3 genes and downregulating the expression levels of BCL-2 gene. Furthermore, both compounds suppress metastasis by reducing cell adhesion and cell migration/invasion by elevating the expression level of E-cadherin and reducing the expression level of P-cadherin and N-cadherin. Additionally, both genistein and 1,25(OH)₂D₃ increased the expression level of ERK1 and reduced the expression levels of JNK, p38, Ras, and MEK proteins, which reduced metastasis, enhanced the response to cancer treatment, and improved overall survival. Thus, genistein and 1,25(OH)₂D₃ can both be considered key candidates in the search for new breast cancer treatments.

Keywords: Apoptosis; Breast cancer; Cell cycle; Genistein; MAPK; Metastasis; Ras pathway; Vitamin D.