Acetyl tributyl citrate attenuates 5-fluorouracil-induced inflammation, oxidative stress, and apoptosis in human keratinocytes.

Autor: Ha Y; Department of Food and Nutrition, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea., Kang W; Department of Food and Nutrition, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea., Roh J; Department of Food and Nutrition, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea., Jung Y; Department of Food and Nutrition, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea., Lee H; Department of Food and Nutrition, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea., Park T; Department of Food and Nutrition, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea. Electronic address: tspark@yonsei.ac.kr.
Jazyk: angličtina
Zdroj: Biochemical pharmacology [Biochem Pharmacol] 2024 Dec; Vol. 230 (Pt 2), pp. 116606. Date of Electronic Publication: 2024 Nov 01.
DOI: 10.1016/j.bcp.2024.116606
Abstrakt: 5-Fluorouracil (5-FU) is a commonly used chemotherapy drug that effectively destroys cancer cells. Despite its widespread use and efficacy, it also presents considerable challenges, particularly with adverse effects on rapidly dividing normal cells, such as keratinocytes. These detrimental effects are attributed to inflammatory, oxidative, and apoptotic potentials, leading to severe skin disorders. Due to the lack of specific remedies for 5-FU-induced dermatological side effects, conventional treatments are applied instead, which provide limited relief and have drawbacks. This study investigated the impact of acetyl tributyl citrate (ATBC) in 5-FU-treated human keratinocytes. The findings indicated that ATBC substantially reduced inflammation caused by 5-FU, as demonstrated by nuclear translocation of nuclear factor kappa B and expression of its downstream genes, including tumor necrosis factor, interleukin 1 beta (IL1B), and IL6. ATBC also markedly decreased oxidative stress, indicated by reactive oxygen species levels and the antioxidant gene expression such as superoxide dismutase 1 (SOD1), SOD2, and heme oxygenase 1 in 5-FU-treated cells. Furthermore, ATBC attenuated 5-FU-induced apoptosis, as determined by lactate dehydrogenase release and Annexin V/propidium iodide flow cytometry, with the potential involvement of interferon-related genes. Following this, protein kinase C delta was predicted as a possible molecular target of ATBC. These findings propose ATBC as a therapeutic agent for managing the cutaneous side effects associated with 5-FU treatment.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Taesun Park has patent pending to Yonsei University. Wesuk Kang has patent pending to Yonsei University. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024. Published by Elsevier Inc.)
Databáze: MEDLINE
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