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Vitamin C Inhibits Lipopolysaccharide-Induced Hyperinflammatory State of Chronic Myeloid Leukemia Cells through Purinergic Signaling and Autophagy.
Pires, Daniela A; Brandão-Rangel, Maysa A R; Silva-Reis, Anamei; Olímpio, Fabiana R S; Aimbire, Flavio; Oliveira, Carlos R; Mateus-Silva, José R; Zamarioli, Lucas S; Bachi, André L L; Bella, Yanesko F; Santos, Juliana M B; Bincoletto, Claudia; Lancha, Antonio Herbert; Vieira, Rodolfo P.
Afiliación
  • Pires DA; Post-Graduation Program in Bioengineering, Universidade Brasil, Rua Carolina Fonseca 235, São Paulo 08230-030, SP, Brazil.
  • Brandão-Rangel MAR; Postgraduate Program in Science of Human Movement and Rehabilitation, Federal University of São Paulo (UNIFESP), Avenida Ana Costa 95, Santos 11060-001, SP, Brazil.
  • Silva-Reis A; Postgraduate Program in Science of Human Movement and Rehabilitation, Federal University of São Paulo (UNIFESP), Avenida Ana Costa 95, Santos 11060-001, SP, Brazil.
  • Olímpio FRS; Department of Medicine, Postgraduate Program in Translational Medicine, Federal University of São Paulo (UNIFESP), Rua Pedro de Toledo 720, Vila Clementino, São Paulo 04039-002, SP, Brazil.
  • Aimbire F; Department of Medicine, Postgraduate Program in Translational Medicine, Federal University of São Paulo (UNIFESP), Rua Pedro de Toledo 720, Vila Clementino, São Paulo 04039-002, SP, Brazil.
  • Oliveira CR; Gap Biotech Laboratory of Biotechnology and Bioinformatics, Rua Comendador Remo Cesaroni 223, São José dos Campos 12243-020, SP, Brazil.
  • Mateus-Silva JR; Gap Biotech Laboratory of Biotechnology and Bioinformatics, Rua Comendador Remo Cesaroni 223, São José dos Campos 12243-020, SP, Brazil.
  • Zamarioli LS; Department of Pharmacology, Federal University of São Paulo (UNIFESP), Rua Três de Maio 100, São Paulo 04044-020, SP, Brazil.
  • Bachi ALL; Postgraduate Program in Health Science, Santo Amaro University, Rua Prof. Enéas de Siqueira Neto 340, São Paulo 04829-300, SP, Brazil.
  • Bella YF; Postgraduate Program in Science of Human Movement and Rehabilitation, Federal University of São Paulo (UNIFESP), Avenida Ana Costa 95, Santos 11060-001, SP, Brazil.
  • Santos JMB; Postgraduate Program in Science of Human Movement and Rehabilitation, Federal University of São Paulo (UNIFESP), Avenida Ana Costa 95, Santos 11060-001, SP, Brazil.
  • Bincoletto C; Department of Pharmacology, Federal University of São Paulo (UNIFESP), Rua Três de Maio 100, São Paulo 04044-020, SP, Brazil.
  • Lancha AH; Experimental Surgery (LIM 26), Laboratory of Clinical Investigation, School of Medicine, University of Sao Paulo, Avenida Doutor Arnaldo 455, São Paulo 05508-030, SP, Brazil.
  • Vieira RP; Post-Graduation Program in Bioengineering, Universidade Brasil, Rua Carolina Fonseca 235, São Paulo 08230-030, SP, Brazil.
Nutrients ; 16(3)2024 Jan 29.
Article en En | MEDLINE | ID: mdl-38337668
ABSTRACT

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 µg/mL and 10 µg/mL) were employed, along with the lysosome inhibitor chloroquine (CQ; 100 µM), administered 2 h prior to LPS stimulation (10 ng/mL) for a duration of 22 h in K-562 cells (3 × 105 cells/mL/well).

Results:

Both doses of vitamin C reduced the release of interleukin-6 (IL-6) (5 µg/mL, p < 0.01 and 10 µg/mL, p < 0.01) and tumor necrosis factor (TNF) (5 µg/mL, p < 0.01 and 10 µg/mL, p < 0.01) induced by LPS. Furthermore, in LPS + CQ-stimulated cells, vitamin C at a concentration of 10 µg/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 µg/mL, p < 0.01 and 10 µg/mL, p < 0.01), while only the 10 µg/mL dose of vitamin C induced the release of Klotho (10 µg/mL, p < 0.01). In addition, both doses of vitamin C reduced the accumulation of ATP (5 µg/mL, p < 0.01 and 10 µg/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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leucemia Mielógena Crónica BCR-ABL Positiva / Lipopolisacáridos Límite: Humans Idioma: En Revista: Nutrients Año: 2024 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Suiza

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Leucemia Mielógena Crónica BCR-ABL Positiva / Lipopolisacáridos Límite: Humans Idioma: En Revista: Nutrients Año: 2024 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Suiza