Polarization of Melatonin-Modulated Colostrum Macrophages in the Presence of Breast Tumor Cell Lines.

Human colostrum and milk contain diverse cells and soluble components that have the potential to act against tumors. In breast cancer, macrophages play a significant role in immune infiltration and contribute to the progression and spread of tumors. However, studies suggest that these cells can be reprogrammed to act as an antitumor immune response. This study aimed to evaluate the levels of melatonin and its receptors, MT1 (melatonin receptor 1) and MT2 (melatonin receptor 2), in colostrum and assess the differentiation and polarization of the colostrum macrophages modulated by melatonin in the presence of breast tumor cells. Colostrum samples were collected from 116 mothers and tested for their melatonin and receptor levels. The colostrum cells were treated with or without melatonin and then cultured for 24 h in the presence or absence of breast tumor cells. The results showed that melatonin treatment increased the expression of MT1 and MT2 in the colostrum cells. Furthermore, melatonin treatment increased the percentage of M1 macrophages and decreased the percentage of M2 macrophages. When the colostrum macrophages were cocultured with breast tumor cells, melatonin reduced the percentage of both macrophage phenotypes and the cytokines tumor necrosis factor-alpha (TNF-α) and interleukin 8 (IL-8). These data suggest that melatonin can regulate the inflammatory process via M1 macrophages in the tumor microenvironment and, simultaneously, the progression of M2 macrophages that favor tumorigenesis.

Bioactive compounds of pequi pulp and oil extracts modulate antioxidant activity and antiproliferative activity in cocultured blood mononuclear cells and breast cancer cells.

BACKGROUND: Pequi (Caryocar brasiliense Camb.) is a fruit from Brazilian Cerrado rich in bioactive compounds, such as phytosterols and tocopherols, which can modulate the death of cancer cells. OBJECTIVE: In the present study, the main bioactive compounds of hydrophilic and lipophilic extracts of pequi oil and pulp were identified and were verified if they exert modulatory effects on oxidative stress of mononuclear cells cocultured with MCF-7 breast cancer cells. STUDY DESIGN: Identification and quantification of the main compounds and classes of bioactive compounds in pequi pulp and oil, hydrophilic, and lipophilic extracts were performed using spectroscopy and liquid chromatographic methods, while the beneficial effects, such as antioxidant capacity in vitro, were determined using methods based on single electron transfer reaction or hydrogen atom transfer, while for antioxidant and antiproliferative activities ex vivo, 20 healthy volunteers were recruited. Human peripheral blood mononuclear cells (MN) were collected, and cellular viability assay by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide), superoxide anion evaluation, and CuZn-superoxide dismutase determination (CuZn-SOD) in MN cells, MCF-7 cells, and coculture of MN cells and MCF-7 cells in the presence and absence of pequi pulp or oil hydrophilic and lipophilic extracts were performed. RESULTS: In the hydrophilic extract, the pequi pulp presented the highest phenolic content, while in the oil lipophilic extract, it had the highest content of carotenoids. The main phytosterol in pequi oil was ß-sitosterol (10.22 mg/g), and the main tocopherol was γ-tocopherol (26.24 µg/g sample). The extracts that had highest content of bioactive compounds stimulated blood mononuclear cells and also improved SOD activity. By evaluating the extracts against MCF-7 cells and coculture, they showed cytotoxic activity. CONCLUSION: The results support the anticarcinogenic activity of pequi extracts, in which the pequi pulp hydrophilic extracts presented better immunomodulatory potential.

Effects of barium chloride adsorbed to polyethylene glycol (PEG) microspheres on co-culture of human blood mononuclear cell and breast cancer cell lines (MCF-7).

This study investigated the effects of BaCl2 adsorbed to polyethylene glycol (PEG) microspheres on human blood mononuclear cells (MN) co-cultured with breast cancer cell lines (MCF-7). The MCF-7 cells were obtained from the American Type Culture Collection and the blood mononuclear (MN) cells from volunteer donors. MN cells, MCF-7 cells and their co-culture (MN and MCF-7 cells) were pre-incubated for 24 h with or without 25 and 1000 pg L-1 BaCl2 (Ba25 and Ba1000), PEG microspheres or 25 and 1000 pg L-1 BaCl2 adsorbed to PEG microspheres (PEG-Ba25 and PEG-Ba1000). Rheological parameters and apoptosis were determined. Fluorescence microscopy and flow cytometry analyses revealed that BaCl2 was able to adsorb the PEG microspheres. The blood flow and viscosity curves were similar among the treatments. In general, apoptosis rates increased in co-cultured cells, co-cultured cells incubated with Ba25 and with PEG-Ba25, but the highest rates were observed in co-cultured cells incubated with PEG-Ba1000. In conclusion, BaCl2 adsorbed to PEG microspheres exhibited dose-dependent antitumor effects against human MCF-7 breast cancer cells co-cultured with MN cells, thereby offering a possible therapeutic alternative for treating this disease provided they are administered at very low concentrations.

Herbal Mixture Adsorbed to Polyethylene Glycol Microspheres Induces Apoptotic Effects on Breast Cancer Cells.

BACKGROUND: The combination of medicinal plants and polymeric matrices raised the possibility of obtaining new drugs to treat a number of diseases, including cancer. Breast cancer is one of the most frequent diseases among women, but the effective treatments is still a challenge. METHODS: Thus, this study investigated the effect of herbal mixture adsorbed to PEG microspheres on MCF-7 human breast cancer cells and these cells in co-culture of blood MN cells. The MCF-7 cells and the blood mononuclear [MN] cells from volunteer donors. MN cells, MCF-7 cells and co-culture [MN and MCF-7 cells] were pre-incubated for 24 h with or without herbal mixture [HM], polyethylene glycol [PEG] microspheres or herbal mixture adsorbed in PEG microspheres [PEG-HM]. Viability, intracellular calcium and apoptosis were determined by flow cytometry. The herbal mixture adsorbed in PEG microspheres reduces the viability of MCF-7 cells. RESULTS: The lowest viability índex was observed in co-culture incubated with herbal mixture adsorbed to PEG microspheres. MN cells, MCF-7 cells and co-culture showed higher intracellular Ca2+ release when incubated with herbal mixture adsorbed to PEG microspheres. The apoptosis index was higher in MCF-7 cells that were treated with herbal mixture. The highest apoptosis index was observed in coculture of these cells incubated with herbal mixture adsorbed to PEG microspheres. CONCLUSION: These data suggest that herbal mixture adsorbed by PEG microspheres has apoptotic effects on human MCF-7 breast cancer cells and is therefore a possible therapeutic alternative.

Intracellular calcium is a target of modulation of apoptosis in MCF-7 cells in the presence of IgA adsorbed to polyethylene glycol.

PURPOSE: Clinical and epidemiological studies have indicated that breastfeeding has a protective effect on breast cancer risk. Protein-based drugs, including antibodies, are being developed to attain better forms of cancer therapy. Secretory IgA (SIgA) is the antibody class in human breast milk, and its activity can be linked to the protective effect of breastfeeding. The aim of this study was to investigate the effect of polyethylene glycol (PEG) microspheres with adsorbed SIgA on MCF-7 human breast cancer cells. METHODS: The PEG microspheres were characterized by flow cytometry and fluorescence microscopy. The MCF-7 cells were obtained from American Type Culture Collection. MCF-7 cells were pre-incubated for 24 hours with or without SIgA (100 ng/mL), PEG microspheres or SIgA adsorbed in PEG microspheres (100 ng/mL). Viability, intracellular calcium release, and apoptosis in MCF-7 cells were determined by flow cytometry. RESULTS: Fluorescence microscopy and flow cytometry analyses revealed that SIgA was able to adsorb to the PEG microspheres. The MCF-7 cells that were incubated with PEG microspheres with adsorbed SIgA showed decreased viability. MCF-7 cells that were incubated with SIgA or PEG microspheres with adsorbed SIgA had increased intracellular Ca(2+) levels. In the presence of SIgA, an increase in the percentage of apoptotic cells was observed. The highest apoptosis index was observed when the cells were treated with PEG microspheres with adsorbed SIgA. CONCLUSION: These data suggest that colostral SIgA adsorbed to PEG microspheres has antitumor effects on human MCF-7 breast cancer cells and that the presence of large amounts of this protein in secreted breast milk may provide protection against breast tumors in women who breastfed.