Brazilian green propolis: A novel tool to improve the cytotoxic and immunomodulatory action of docetaxel on MCF-7 breast cancer cells and on women monocyte.

Docetaxel (DTX) is used against breast cancer despite its side effects such as toxicity and immunosuppression. Here we investigated the cytotoxic and immunomodulatory effects of the ethanol solution extract of propolis (EEP) in combination with DTX on MCF-7 breast cancer cells and on women's monocyte. The cytotoxic potential of EEP + DTX was assessed by MTT assay and the type of tumor cell death was evaluated by flow cytometry. The effects of EEP + DTX on the migration and invasion of MCF-7 cells were analyzed. Cytokine production by monocytes was assessed by ELISA and the expression of cell surface markers was evaluated by flow cytometry. We also assessed the fungicidal activity of monocytes against Candida albicans and the generation of reactive oxygen species (ROS). Finally, the impact of the supernatants of treated monocytes in the viability, migration, and invasiveness of tumor cells was assessed. EEP enhanced the cytotoxicity of DTX alone against MCF-7 cells by inducing necrosis and inhibiting their migratory ability. EEP + DTX exerted no cytotoxic effects on monocytes and stimulated HLA-DR expression, TNF-α, and IL-6 production, exerted an immunorestorative action in the fungicidal activity, and reduced the oxidative stress. Our findings have practical implications and reveal new insights for complementary medicine.

The long non-coding RNA ANRASSF1 in the regulation of alternative protein-coding transcripts RASSF1A and RASSF1C in human breast cancer cells: implications to epigenetic therapy.

Alternative protein-coding transcripts of the RASSF1 gene have been associated with dual functions in human cancer: while RASSF1C isoform has oncogenic properties, RASSF1A is a tumour suppressor frequently silenced by hypermethylation. Recently, the antisense long non-coding RNA RASSF1 (ANRASSF1) was implicated in a locus-specific mechanism for the RASSF1A epigenetic repression mediated by PRC2 (Polycomb Repressive Complex 2). Here, we evaluated the methylation patterns of the promoter regions of RASSF1A and RASSF1C and the expression levels of these RASSF1 transcripts in breast cancer and breast cancer cell lines. As expected, RASSF1C remained unmethylated and RASSF1A was hypermethylated at high frequencies in 75 primary breast cancers, and also in a panel of three mammary epithelial cells (MEC) and 10 breast cancer cell lines (BCC). Although RASSF1C was expressed in all cell lines, only two of them expressed the transcript RASSF1A. ANRASSF1 expression levels were increased in six BCCs. In vitro induced demethylation with 5-Aza-2'-deoxicytydine (5-Aza-dC) resulted in up-regulation of RASSF1A and an inverse correlation with ANRASSF1 relative abundance in BCCs. However, increased levels of both transcripts were observed in two MECs (184A1 and MCF10A) after treatment with 5-Aza-dC. Overall, these findings indicate that ANRASSF1 is differentially expressed in MECs and BCCs. The lncRNA ANRASSF1 provides new perspectives as a therapeutic target for locus-specific regulation of RASSF1A.