Posted by 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, MβCD modified with mannose (Man-MβCD) was prepared 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 (the oncrease in LC-3 expression in the tumor tissues) 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.
Yoshitaka Ohno, Maiko Toshino, Ahmed F.A. Mohammed, Yukio Fujiwara, Yoshihiro Komohara, Risako Onodera, Taishi Higashi, Keiichi Motoyama (2023) Mannose-methyl-β-cyclodextrin suppresses tumor growth by targeting both colon cancer cells and tumor-associated macrophages. Carbohydrate Polymers 305, 120551. https://doi.org/10.1016/j.carbpol.2023.120551.