Chloramphenicol alleviates 5-fluorouracil-induced cellular senescence through activation of autophagy.
| Autor: | Bai S; School of Basic Medicine, Dali University, Dali, Yunnan 671000, China., Zhao Q; School of Basic Medicine, Dali University, Dali, Yunnan 671000, China., Jia H; School of Basic Medicine, Dali University, Dali, Yunnan 671000, China., He F; School of Basic Medicine, Dali University, Dali, Yunnan 671000, China., Wang X; School of Basic Medicine, Dali University, Dali, Yunnan 671000, China. |
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| Jazyk: | angličtina |
| Zdroj: | Canadian journal of physiology and pharmacology [Can J Physiol Pharmacol] 2024 Nov 01; Vol. 102 (11), pp. 661-671. Date of Electronic Publication: 2024 May 22. |
| DOI: | 10.1139/cjpp-2023-0432 |
| Abstrakt: | 5-Fluorouracil (5-FU) is a first-line treatment for colorectal cancer, but side effects such as severe diarrhea are common in clinical use and have been linked to its induction of normal cell senescence. Chloramphenicol (CAP) is an antibiotic commonly used to treat typhoid or anaerobic infections, but its senescence-related aspects have not been thoroughly investigated. Here, we used 5-FU to induce senescence in human umbilical vein endothelial cells (HUVECs) and investigated the relationship between CAP and cellular senescence at the cellular level. In a model of cellular senescence induced by 5-FU treatment, we discovered that CAP treatment reversed the rise in the percentage of senescence-associated galactosidase (SA-β-gal)-positive cells and decreased the expression of senescence-associated proteins (p16), senescence-associated genes (p21), and senescence-associated secretory phenotypes (SASPs: IL-6, TNF-α). In addition, CAP subsequently restored the autophagic process inhibited by 5-FU and upregulated the levels of autophagy-related proteins. Mechanistically, we found that CAP restored autophagic flux by inhibiting the mTOR pathway, which in turn alleviated FU-induced cellular senescence. Our findings suggest that CAP may help prevent cellular senescence and restore autophagy, opening up new possibilities and approaches for the clinical management of colorectal cancer. Competing Interests: The authors declare that they do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted. |
| Databáze: | MEDLINE |
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