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

Honório-França, Adenilda Cristina; Nunes, Gabriel Triches; Fagundes, Danny Laura Gomes; Marchi, Patrícia Gelli Feres de; Fernandes, Rubian Trindade da Silva; França, Juliana Luzia; França-Botelho, Aline do Carmo; Moraes, Lucélia Campelo Albuquerque; Varotti, Fernando de Pilla; França, Eduardo Luzía

doi:10.2147/ott.s99839

Cited by 19 publications

(12 citation statements)

References 46 publications

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“…In constrast, MET treatment induced if Ca 2+ upregulation in both MOs and co-culture systems. Our findings support simultaneous MO activation and the induction of apoptosis in breast cancer cells as suggested previously (59,62,63).…”

Section: Discussionsupporting

confidence: 92%

Phenotypic functional activities of monocyte change during crosstalk with breast cancer cell and enhancing effect of metformin of IFN-γ-associated antitumor cytokine production

Dahmani

Addou-Klouche

Gizard

et al. 2020

Preprint

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Background: Immune activities of monocytes (MOs) can be altered within the microenvironment of solid malignancies, including breast cancer. Metformin (1,1dimethylbiguanide hydrochloride, MET), has been shown to decrease tumor cell proliferation, but its effects have yet to be explored with respect to the crosstalk between monocytes and breast cancer cells. Here, we investigated the effects of MET on overall phenotypic functional activities of autologous MOs during the interplay with primary breast cancer cells. Methods:Human primary breast cancer cells were either cultured alone or co-cultured with autologous MOs before treatment with MET.Results: MET downregulated both breast cancer cell proliferation and the ratio of phosphorylated Akt (p-Akt)-to-Akt in breast cancer cells. Additionally, we observed that, in the absence of MET treatment, the levels of LDH-based cytotoxicity, catalase, intracellular free calcium ions (i fCa 2+ ), IL-10 and arginase activity were significantly reduced in co-cultures compared to those of MOs cultivated alone whereas levels of iNOS were significantly increased (for all comparisons, p < 0.05). In contrast, MET upregulated breast cancer cell LDH-based cytotoxicity levels when co-cultured with MO. MET also induced upregulation of both the inducible enzymatic activity of nitric oxide synthase (iNOS) and arginase activity in MO cells and co-culture systems, although these differences did not reach significant levels for iNOS activity (p > 0.05). MET greatly decreased phagocytic activity in isolated MOs while inducing a robust increase of catalase activity in co-culture systems and of superoxide dismutase (SOD) activity in MOs, but not in MOs co-cultured with breast cancer cells. MET strongly upregulated the levels of ifCa 2+ in co-culture systems and IFN-γ production in both isolated MOs and co-culture systems. Moreover, MET treatment markedly downregulated IL-10 production in MOs, while inducing a slight increase in co-cultures (p > 0.05). Conclusions: Our results show that the phenotypic functional activities of MOs change when co-cultured with primary human breast cancer cells. Furthermore, treatment with MET induced enhancing effects on the production of antitumor cytokine IFN-γ and ifCa 2+ , as well as cytotoxicity during breast cancer cell-MO crosstalk. Keywords: Akt activation; metformin; monocyte/primary human breast cancer cell crosstalk; monocyte phenotypic functional activity changes; primary breast cancer cell proliferation and viability; MO IFN-γ-associated anti-tumor activity

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Section: Discussionsupporting

confidence: 92%

Phenotypic functional activities of monocyte change during crosstalk with breast cancer cell and enhancing effect of metformin of IFN-γ-associated antitumor cytokine production

Dahmani

Addou-Klouche

Gizard

et al. 2020

Preprint

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“…Changes in intracellular Ca2 + release by human cells may result in cell damage and activation of cell death pathways [45], and the release of large amounts of intracellular Ca2 + has been associated with induction of apoptosis in human cells. [13,44,46]. In this work, independent of the phases of day, the highest levels of apoptosis were observed in cells in the presence of melatonin adsorbed to the PEG microsphere, and the most expressive apoptosis was observed in the co-cultures.…”

Section: Discussionsupporting

confidence: 48%

“…Cancer development and progression is characterized by dynamic changes in the expression and function of protein kinases [42] or their signaling pathways, which can lead to malignant transformation of breast cells [43]. Studies have reported that a modified release system with antibodies [44] or melatonin [13] are capable of activating the signaling pathways involving calcium intracellular mechanisms and of inducing apoptosis in breast cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Nanodoses of melatonin induces apoptosis on human breast cancer cells co-cultured with colostrum cells

2019

Biointerface Res Appl Chem

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The aim of this study was to investigate the effect of melatonin nanodoses adsorbed to PEG microspheres during different phases of the day on oxidative stress and apoptosis in human colostrum mononuclear (MN) cells co-cultured with breast cancer tumor cells (MCF-7). The MCF-7 cells were obtained from the American Type Culture Collection, and the MN cells were obtained from volunteer donors. The cells were preincubated for 24 h with or without 100 ng.mL-1 melatonin (MLT), PEG microspheres (PEG) or 100 ng.mL-1 MLT adsorbed to PEG microspheres (PEG-MLT). Superoxide, superoxide dismutase (SOD), intracellular calcium and apoptosis in the MN cells, MCF-7 cells and co-cultures were determined. The MN cells and co-cultured cells during the nocturnal period and the MCF-7 cells during the diurnal period exhibited increased superoxide release in the presence of PEG-MLT. MN cells treated with MLT during both periods of the day exhibited the highest SOD concentrations, whereas the MCF-7 cells had high SOD levels when incubated with PEG-MLT during the nocturnal period. The nocturnal period co-culture, independent of treatment, showed the highest levels of the enzyme. The highest amount of intracellular Ca2+ release was observed in MN cells and MCF-7 cells co-cultured with PEG-MLT during the nocturnal period. Irrespective of the phase of the day, the highest apoptosis index was observed in co-cultures of cells incubated with MLT-PEG. These data suggest that nanodoses of melatonin-modified release plus physiological melatonin produced in higher concentrations during the night can increase the effective activity of this hormone against tumors.

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“…if Ca 2+ is an important secondary messenger that regulates various cellular processes and signaling pathways including those related to cancer, such as apoptosis, proliferation and metastasis [ 67 , 68 ], and those involved in immune responses of MOs, including the production of cytokines and phagocytic activation [ 69 , 70 ]. We first observed that if Ca 2+ levels were reduced in co-culture of MOs with breast cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Metformin partially reverses the inhibitory effect of co-culture with ER-/PR-/HER2+ breast cancer cells on biomarkers of monocyte antitumor activity

et al. 2020

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Background Immune activities of monocytes (MOs) can be altered within the microenvironment of solid malignancies, including breast cancer. Metformin (1,1-dimethylbiguanide hydrochloride, MET), has been shown to decrease tumor cell proliferation, but its effects have yet to be explored with respect to MOs (monocytes) activity during their crosstalk with breast cancer cells. Here, we investigated the effects of MET on overall phenotypic functional activities, including cellular immunometabolism and protective redox signaling based-biomarkers, intracellular free calcium ions ( if Ca 2+ ), phagocytosis and co-operative cytokines (IFN-γ and IL-10) of autologous MOs before and during their interplay with primary ER - /PR - /HER2 + breast cancer cells. Methods Human primary breast cancer cells were either cultured alone or co-cultured with autologous MOs before treatment with MET. Results MET downregulated breast cancer cell proliferation and phagocytosis, while having no significant effect on the ratio of phosphorylated Akt (p-Akt) to total Akt. Additionally, we observed that, in the absence of MET treatment, the levels of lactate dehydrogenase (LDH)-based cytotoxicity, catalase, if Ca 2+ , IL-10 and arginase activity were significantly reduced in co-cultures compared to levels in MOs cultured alone whereas levels of inducible nitric oxide synthase (iNOS) activity were significantly increased. In contrast, MET treatment reduced the effects measured in co-culture on the levels of LDH-based cytotoxicity, arginase activity, catalase, if Ca 2+ , and IFN-γ. MET also induced upregulation of both iNOS and arginase in MO cells, although the increase did not reach significant difference for iNOS activity. Moreover, MET induced a robust increase of superoxide dismutase (SOD) activity in MOs, but not in MOs co-cultured with breast cancer cells. Furthermore, MET markedly upregulated the levels of IFN-γ production and downregulated those of IL-10 in isolated MOs, while inducing a slight opposing up-regulation of IL-10 production in co-cultures. Conclusions Our results show that the biomarkers of phenotypic functional activities of MOs are modified after co-culturing with primary human breast cancer cells. Treatment of co-cultures with MET resulted in increased release of antitumor cytokine IFN-γ and if Ca 2+ , and increased cell necrosis during breast cancer cells-MOs crosstalk.

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

Cited by 19 publications

References 46 publications

Phenotypic functional activities of monocyte change during crosstalk with breast cancer cell and enhancing effect of metformin of IFN-γ-associated antitumor cytokine production

Phenotypic functional activities of monocyte change during crosstalk with breast cancer cell and enhancing effect of metformin of IFN-γ-associated antitumor cytokine production

Nanodoses of melatonin induces apoptosis on human breast cancer cells co-cultured with colostrum cells

Metformin partially reverses the inhibitory effect of co-culture with ER-/PR-/HER2+ breast cancer cells on biomarkers of monocyte antitumor activity

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