Kaurenoic acid nanocarriers regulates cytokine production and inhibit breast cancer cell migration.

Autor: Ferreira KCB; Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal de Juiz de Fora, Juiz de Fora 36036-900, Minas Gerais, Brazil., Valle ABCDS; Programa de Pós-Graduação em Ciências Biológicas, Universidade Federal de Juiz de Fora, Juiz de Fora 36036-900, Minas Gerais, Brazil., Gualberto ACM; Programa de Pós-Graduação em Ciências Biológicas, Universidade Federal de Juiz de Fora, Juiz de Fora 36036-900, Minas Gerais, Brazil., Aleixo DT; Programa de Pós-Graduação em Ciências Biológicas, Universidade Federal de Juiz de Fora, Juiz de Fora 36036-900, Minas Gerais, Brazil., Silva LM; Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal de Juiz de Fora, Juiz de Fora 36036-900, Minas Gerais, Brazil., Santos MM; Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal de Juiz de Fora, Juiz de Fora 36036-900, Minas Gerais, Brazil., Costa DS; Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal de Juiz de Fora, Juiz de Fora 36036-900, Minas Gerais, Brazil., Oliveira LL; Programa de Pós-Graduação em Ciências Biológicas, Universidade Federal de Juiz de Fora, Juiz de Fora 36036-900, Minas Gerais, Brazil., Gameiro J; Programa de Pós-Graduação em Ciências Biológicas, Universidade Federal de Juiz de Fora, Juiz de Fora 36036-900, Minas Gerais, Brazil., Tavares GD; Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal de Juiz de Fora, Juiz de Fora 36036-900, Minas Gerais, Brazil., da Silva Filho AA; Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal de Juiz de Fora, Juiz de Fora 36036-900, Minas Gerais, Brazil., Corrêa JODA; Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal de Juiz de Fora, Juiz de Fora 36036-900, Minas Gerais, Brazil., Pittella F; Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal de Juiz de Fora, Juiz de Fora 36036-900, Minas Gerais, Brazil; Programa de Pós-Graduação em Ciências Biológicas, Universidade Federal de Juiz de Fora, Juiz de Fora 36036-900, Minas Gerais, Brazil. Electronic address: frederico.pittella@ufjf.br.
Jazyk: angličtina
Zdroj: Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2022 Dec; Vol. 352, pp. 712-725. Date of Electronic Publication: 2022 Nov 10.
DOI: 10.1016/j.jconrel.2022.10.048
Abstrakt: Breast cancer is the type of cancer with the highest incidence in women around the world. Noteworthy, the triple-negative subtype affects 20% of the patients while presenting the highest death rate among subtypes. This is due to its aggressive phenotype and the capability of invading other tissues. In general, tumor-associated macrophages (TAM) and other immune cells, are responsible for maintaining a favorable tumor microenvironment for inflammation and metastasis by secreting several mediators such as pro-inflammatory cytokines IL-1β, IL-6, and TNF-α, chemokines like CCL2, and other proteins, as metalloproteinases of matrix (MMP). On the other hand, immunomodulatory agents can interfere in the immune response of TAM and change the disease prognosis. In this work, we prepared nanostructured lipid carriers containing kaurenoic acid (NLC-KA) to evaluate the effect on cytokine production in vitro of bone marrow-derived macrophages (BMDM) and the migratory process of 4 T1 breast cancer cells. NLC-KA prepared from a blend of natural lipids was shown to have approximately 90 nm in diameter with low polydispersity index. To test the effect on cytokine production in vitro in NLC-KA treated BMDM, ELISA assay was performed and pro-inflammatory cytokines IL-1β, IL-6, and TNF-α were quantified. The formulation reduced the secretion of IL-1β and TNF-α cytokines while presenting no hemolytic activity. Noteworthy, an anti-migratory effect in 4 T1 breast cancer cells treated with NLC-KA was observed in scratch assays. Further, MMP9 and CCL2 gene expressions in both BMDM and 4 T1 treated cells confirmed that the mechanism of inhibition of migration is related to the blockade of this pathway by KA. Finally, cell invasion assays confirmed that NLC-KA treatment resulted in less invasiveness of 4 T1 cells than control, and it is independent of CCL2 stimulus or BMDM direct stimulus. Ultimately, NLC-KA was able to regulate the cytokine production in vitro and reduce the migration of 4 T1 breast cancer cells by decreasing MMP9 gene expression.
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Databáze: MEDLINE
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