Mannose-methyl-β-cyclodextrin suppresses tumor growth by targeting both colon cancer cells and tumor-associated macrophages. (1st April 2023)

• Record Type: Journal Article
• Authors: Ohno, Yoshitaka; Toshino, Maiko; Mohammed, Ahmed F.A.; Fujiwara, Yukio; Komohara, Yoshihiro; Onodera, Risako; Higashi, Taishi; Motoyama, Keiichi
• Is Part Of: Carbohydrate polymers. Volume 305(2023)
• Publication Date: 2023-04-01
• Subjects: Cyclodextrin -- Mannose -- Autophagy -- Antitumor drug -- Colorectal cancer; Polysaccharides -- Periodicals; Polysaccharides -- Periodicals; Polysaccharides -- Périodiques; Electronic journals; 547.78
• DOI: 10.1016/j.carbpol.2023.120551
• Languages: English
• ISSNs: 0144-8617

Abstract

Abstract: Methylated β-cyclodextrin (MβCD) can extract cholesterol from lipid rafts and induce apoptosis in cancer cells by inhibiting activation of the PI3K-Akt-Bad pathway. In this study, we modified MβCD with mannose (Man-MβCD) and assessed its in vitro and in vivo potential for targeting colon cancer cells expressing the mannose receptor (MR) and tumor-associated macrophages (TAM). Man-MβCD showed a significantly greater level of cellular association with colon-26 cells and M2 macrophages, and much more prominent anticancer activity than that of MβCD against MR-positive colon-26 cells. These results revealed that autophagy was the main mechanism of cell death associated with Man-MβCD. Furthermore, compared with MβCD, Man-MβCD significantly reduced tumor development following intravenous delivery to tumor-bearing mice, with no apparent side effects. Thus, Man-MβCD has the potential to be a novel anticancer drug. Graphical abstract: Unlabelled Image