Vitamin C Inhibits Lipopolysaccharide-Induced Hyperinflammatory State of Chronic Myeloid Leukemia Cells through Purinergic Signaling and Autophagy

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Tipo de produção
article
Data de publicação
2024
Título da Revista
ISSN da Revista
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Editora
MDPI
Autores
PIRES, Daniela A.
BRANDAO-RANGEL, Maysa A. R.
SILVA-REIS, Anamei
OLIMPIO, Fabiana R. S.
AIMBIRE, Flavio
OLIVEIRA, Carlos R.
MATEUS-SILVA, Jose R.
ZAMARIOLI, Lucas S.
BACHI, Andre L. L.
BELLA, Yanesko F.
Citação
NUTRIENTS, v.16, n.3, article ID 383, 14p, 2024
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Background: Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by the overproduction of white blood cells, leading to symptoms such as fatigue, infections, and other complications. CML patients must take measures to prevent infections to mitigate the exacerbation of cancer cell proliferation and comorbidities. Methods: This study investigated whether vitamin C can suppress the hyperinflammatory activation of K-562 cells induced by lipopolysaccharide (LPS) and whether purinergic signaling (ATP and P2X7 receptor) and autophagy play a role in it. Two different doses of vitamin C (5 mu g/mL and 10 mu g/mL) were employed, along with the lysosome inhibitor chloroquine (CQ; 100 mu M), administered 2 h prior to LPS stimulation (10 ng/mL) for a duration of 22 h in K-562 cells (3 x 10(5) cells/mL/well). Results: Both doses of vitamin C reduced the release of interleukin-6 (IL-6) (5 mu g/mL, p < 0.01 and 10 <mu>g/mL, p < 0.01) and tumor necrosis factor (TNF) (5 <mu>g/mL, p < 0.01 and 10 <mu>g/mL, p < 0.01) induced by LPS. Furthermore, in LPS + CQ-stimulated cells, vitamin C at a concentration of 10 <mu>g/mL inhibited the expression of LC3-II (p < 0.05). Conversely, both doses of vitamin C led to the release of the anti-inflammatory cytokine interleukin-10 (IL-10) (5 <mu>g/mL, p < 0.01 and 10 <mu>g/mL, p < 0.01), while only the 10 <mu>g/mL dose of vitamin C induced the release of Klotho (10 mu g/mL, p < 0.01). In addition, both doses of vitamin C reduced the accumulation of ATP (5 <mu>g/mL, p < 0.01 and 10 <mu>g/mL, p < 0.01) and decreased the expression of the P2X7 receptor at the mRNA level. Conclusions: Vitamin C inhibits the hyperinflammatory state induced by LPS in K-562 cells, primarily by inhibiting the ATP accumulation, P2X7 receptor expression, and autophagy signaling.
Palavras-chave
ascorbic acid, vitamin C, purinergic signaling, leukemia, autophagy, inflammation
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