Role of poly(ε-caprolactone) lipid-core nanocapsules on melanoma–neutrophil crosstalk
Carine C Drewes,1 Aline de CS Alves,2,3 Cristina B Hebeda,1 Isabela Copetti,2,3 Silvana Sandri,1 Mayara K Uchiyama,4 Koiti Araki,4 Silvia S Guterres,2 Adriana R Pohlmann,2,3 Sandra H Farsky1 1Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of S&a...
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Dove Medical Press
2017
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oai:doaj.org-article:d717e95005db4c67b428bc4ed0dc5a5d2021-12-02T01:01:50ZRole of poly(ε-caprolactone) lipid-core nanocapsules on melanoma–neutrophil crosstalk1178-2013https://doaj.org/article/d717e95005db4c67b428bc4ed0dc5a5d2017-09-01T00:00:00Zhttps://www.dovepress.com/role-of-polye-caprolactone-lipid-core-nanocapsules-on-melanoma-neutrop-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Carine C Drewes,1 Aline de CS Alves,2,3 Cristina B Hebeda,1 Isabela Copetti,2,3 Silvana Sandri,1 Mayara K Uchiyama,4 Koiti Araki,4 Silvia S Guterres,2 Adriana R Pohlmann,2,3 Sandra H Farsky1 1Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, 2Postgraduate Program in Pharmaceutical Sciences, 3Department of Organic Chemistry, Institute of Chemistry, Federal University of Rio Grande do Sul, Porto Alegre, 4Department of Fundamental Chemistry, Institute of Chemistry, University of São Paulo, São Paulo, Brazil Abstract: Metastatic melanoma is an aggressive cancer with increasing incidence and limited therapies in advanced stages. Systemic neutrophilia or abundant neutrophils in the tumor contribute toward its worst prognosis, and the interplay of cancer and the immune system has been shown in tumor development and metastasis. We recently showed the in vivo efficacy of poly(ε-caprolactone) lipid-core nanocapsule (LNC) or LNC loaded with acetyleugenol (AcE-LNC) to treat B16F10-induced melanoma in mice. In this study, we investigated whether LNC or AcE-LNC toxicity could involve modifications on crosstalk of melanoma cells and neutrophils. Therefore, melanoma cells (B16F10) were pretreated with vehicle, LNC, AcE or AcE-LNC for 24 h, washed and, further, cocultured for 18 h with peritoneal neutrophils obtained from C57Bl/6 mice. Melanoma cells were able to internalize the LNC or AcE-LNC after 2 h of incubation. LNC or AcE-LNC pretreatments did not cause melanoma cells death, but led melanoma cells to be more susceptible to death in serum deprivation or hypoxia or in the presence of neutrophils. Interestingly, the production of reactive oxygen species (ROS), which causes cell death, was increased by neutrophils in the presence of LNC- and AcE-LNC-pretreated melanoma cells. LNC or AcE-LNC treatments reduced the concentration of transforming growth factor-β (TGF-β) in the supernatant of melanoma cells, a known factor secreted by cancer cells to induce pro-tumoral actions of neutrophils in the tumor microenvironment. In addition, we found reduced levels of pro-tumoral chemical mediators VEGF, arginase-1, interleukin-10 (IL-10) and matrix metalloproteinase-9 (MMP-9) in the supernatant of LNC or AcE-LNC-pretreated melanoma cells and cocultured with neutrophils. Overall, our data show that the uptake of LNC or AcE-LNC by melanoma cells affects intracellular mechanisms leading to more susceptibility to death and also signals higher neutrophil antitumoral activity. Keywords: hypoxia, serum deprivation, apoptosis, coculture, tumor microenvironment, LNC, acetyleugenol, intravital microscopyDrewes CCAlves ACSHebeda CBCopetti ISandri SUchiyama MKAraki KGuterres SSPohlmann, ARFarsky SHDove Medical PressarticleHypoxiaserum deprivationapoptosisco-culturetumor microenvironmentlipid-core nanocapsulesacetyleugenolintravital microscopyMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 7153-7163 (2017) |
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Hypoxia serum deprivation apoptosis co-culture tumor microenvironment lipid-core nanocapsules acetyleugenol intravital microscopy Medicine (General) R5-920 |
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Hypoxia serum deprivation apoptosis co-culture tumor microenvironment lipid-core nanocapsules acetyleugenol intravital microscopy Medicine (General) R5-920 Drewes CC Alves ACS Hebeda CB Copetti I Sandri S Uchiyama MK Araki K Guterres SS Pohlmann, AR Farsky SH Role of poly(ε-caprolactone) lipid-core nanocapsules on melanoma–neutrophil crosstalk |
| description |
Carine C Drewes,1 Aline de CS Alves,2,3 Cristina B Hebeda,1 Isabela Copetti,2,3 Silvana Sandri,1 Mayara K Uchiyama,4 Koiti Araki,4 Silvia S Guterres,2 Adriana R Pohlmann,2,3 Sandra H Farsky1 1Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, 2Postgraduate Program in Pharmaceutical Sciences, 3Department of Organic Chemistry, Institute of Chemistry, Federal University of Rio Grande do Sul, Porto Alegre, 4Department of Fundamental Chemistry, Institute of Chemistry, University of São Paulo, São Paulo, Brazil Abstract: Metastatic melanoma is an aggressive cancer with increasing incidence and limited therapies in advanced stages. Systemic neutrophilia or abundant neutrophils in the tumor contribute toward its worst prognosis, and the interplay of cancer and the immune system has been shown in tumor development and metastasis. We recently showed the in vivo efficacy of poly(ε-caprolactone) lipid-core nanocapsule (LNC) or LNC loaded with acetyleugenol (AcE-LNC) to treat B16F10-induced melanoma in mice. In this study, we investigated whether LNC or AcE-LNC toxicity could involve modifications on crosstalk of melanoma cells and neutrophils. Therefore, melanoma cells (B16F10) were pretreated with vehicle, LNC, AcE or AcE-LNC for 24 h, washed and, further, cocultured for 18 h with peritoneal neutrophils obtained from C57Bl/6 mice. Melanoma cells were able to internalize the LNC or AcE-LNC after 2 h of incubation. LNC or AcE-LNC pretreatments did not cause melanoma cells death, but led melanoma cells to be more susceptible to death in serum deprivation or hypoxia or in the presence of neutrophils. Interestingly, the production of reactive oxygen species (ROS), which causes cell death, was increased by neutrophils in the presence of LNC- and AcE-LNC-pretreated melanoma cells. LNC or AcE-LNC treatments reduced the concentration of transforming growth factor-β (TGF-β) in the supernatant of melanoma cells, a known factor secreted by cancer cells to induce pro-tumoral actions of neutrophils in the tumor microenvironment. In addition, we found reduced levels of pro-tumoral chemical mediators VEGF, arginase-1, interleukin-10 (IL-10) and matrix metalloproteinase-9 (MMP-9) in the supernatant of LNC or AcE-LNC-pretreated melanoma cells and cocultured with neutrophils. Overall, our data show that the uptake of LNC or AcE-LNC by melanoma cells affects intracellular mechanisms leading to more susceptibility to death and also signals higher neutrophil antitumoral activity. Keywords: hypoxia, serum deprivation, apoptosis, coculture, tumor microenvironment, LNC, acetyleugenol, intravital microscopy |
| format |
article |
| author |
Drewes CC Alves ACS Hebeda CB Copetti I Sandri S Uchiyama MK Araki K Guterres SS Pohlmann, AR Farsky SH |
| author_facet |
Drewes CC Alves ACS Hebeda CB Copetti I Sandri S Uchiyama MK Araki K Guterres SS Pohlmann, AR Farsky SH |
| author_sort |
Drewes CC |
| title |
Role of poly(ε-caprolactone) lipid-core nanocapsules on melanoma–neutrophil crosstalk |
| title_short |
Role of poly(ε-caprolactone) lipid-core nanocapsules on melanoma–neutrophil crosstalk |
| title_full |
Role of poly(ε-caprolactone) lipid-core nanocapsules on melanoma–neutrophil crosstalk |
| title_fullStr |
Role of poly(ε-caprolactone) lipid-core nanocapsules on melanoma–neutrophil crosstalk |
| title_full_unstemmed |
Role of poly(ε-caprolactone) lipid-core nanocapsules on melanoma–neutrophil crosstalk |
| title_sort |
role of poly(ε-caprolactone) lipid-core nanocapsules on melanoma–neutrophil crosstalk |
| publisher |
Dove Medical Press |
| publishDate |
2017 |
| url |
https://doaj.org/article/d717e95005db4c67b428bc4ed0dc5a5d |
| work_keys_str_mv |
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