Triple-negative breast cancer (TNBC) constitutes an important histological subtype of breast cancer with a highly metastatic phenotype. The aim of the current study was to investigate the possible synergism between dendrosomal nanocurcumin (DNC) and exogenously delivered p53 in producing anticancer effects on a TNBC cell line. MTT assay was exploited to determine the viability of MDA-MB-231 cells against DNC and measure the impact of p53 overexpresssion on DNC-related cytotoxicity. Annexin-V/PI staining followed by flow cytometry and wound healing assay were used to evaluate the effects of DNC and exogenous p53, alone and in combination, on apoptosis induction and migratory capacity of MDA-MB-231 cells, respectively. Also, quantitative real-time PCR was applied to analyze the transcript levels of EMT- and metastasis-associated genes. Cell viability measurements demonstrated that DNC suppresses the proliferation of MDA-MB-231 cells in a time- and dose-dependent mode and exogenous p53 elevates the sensitivity of cells to DNC-mediated cytotoxic effects. Apoptosis and wound healing assays indicated that combination treatment with DNC and exogenous p53 leads to significantly increased apoptosis and decreased migration of breast cancer cells, compared with single treatment. The results of gene expression analysis highlighted the high potency of combination strategy to significantly reduce the expression of ZEB1 and BMI1 transcript levels. Altogether, our findings reveal that DNC and exogenous p53 act in a synergistic manner to elicit anticancer effects on MDA-MB-231 breast cancer cells. Therefore, our combination approach might be considered as a promising strategy for the development of new therapeutic modalities against breast cancer.
Keywords: Breast cancer; Dendrosomal nanocurcumin; MDA-MB-231 cell; Synergism; p53.
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