Reduction of Chemoresistance by Claudin-14-Targeting Peptide in Human Colorectal Cancer Cells.

Autor: Mizukami Y; Department of Biopharmaceutical Sciences, Laboratory of Biochemistry, Gifu Pharmaceutical University, Gifu, Japan., Hashimoto S; Department of Biopharmaceutical Sciences, Laboratory of Biochemistry, Gifu Pharmaceutical University, Gifu, Japan., Ando T; Department of Biopharmaceutical Sciences, Laboratory of Biochemistry, Gifu Pharmaceutical University, Gifu, Japan., Ishikawa Y; Faculty of Pharmaceutical Sciences, Shonan University of Medical Sciences, Totsuka-ku, Yokohama, Japan., Eguchi H; Department of Biopharmaceutical Sciences, Laboratory of Biochemistry, Gifu Pharmaceutical University, Gifu, Japan., Yoshino Y; Department of Biopharmaceutical Sciences, Laboratory of Biochemistry, Gifu Pharmaceutical University, Gifu, Japan., Matsunaga T; Laboratory of Bioinformatics, Gifu Pharmaceutical University, Gifu, Japan., Matsuhashi N; Department of Gastroenterological Surgery, Pediatric Surgery, Gifu Graduate School of Medicine, Gifu, Japan., Ikari A; Department of Biopharmaceutical Sciences, Laboratory of Biochemistry, Gifu Pharmaceutical University, Gifu, Japan.
Jazyk: angličtina
Zdroj: Journal of cellular biochemistry [J Cell Biochem] 2024 Nov 20, pp. e30675. Date of Electronic Publication: 2024 Nov 20.
DOI: 10.1002/jcb.30675
Abstrakt: The expression of claudins (CLDNs), major components of tight junctions (TJs), is abnormal in various solid tumors. CLDN14 is highly expressed in human colorectal cancer (CRC) tissues and confers chemoresistance. CLDN14 may become a novel therapeutic target for CRC, but CLDN14-targeting drugs have not been developed. Here, we searched for a CLDN14-targeting peptide, which can suppress CLDN14 expression and chemoresistance using human CRC-derived DLD-1 and LoVo cells. Among some short peptides which mimic the second extracellular loop structure of CLDN14, PSGMK most strongly suppressed the protein expression of CLDN14. The mRNA expression of other endogenous TJ components was unchanged by PSGMK. The PSGMK-induced reduction of CLDN14 protein was inhibited by chloroquine, a lysosome inhibitor, and monodansylcadaverine, a clathrin-dependent endocytosis inhibitor, indicating that PSGMK may enhance endocytosis and lysosomal degradation of CLDN14. In a three-dimensional culture model, the oxidative stress was significantly reduced by PSGMK, whereas hypoxia stress was not. Furthermore, the expression levels of nuclear factor erythroid 2-related factor 2, an oxidative stress response factor, and its target genes were decreased by PSGMK. These results suggest that PSGMK relieves stress conditions in spheroids. The cell viability of spheroids was decreased by anticancer drugs such as doxorubicin and oxaliplatin, which was exaggerated by the cotreatment with PSGMK. Our data indicate that CLDN14-targeting peptide, PSGMK has an anti-chemoresistance effect in CRC cells.
(© 2024 Wiley Periodicals LLC.)
Databáze: MEDLINE
Externí odkaz: