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