Mannose-methyl-β-cyclodextrin suppresses tumor growth by targeting both colon cancer cells and tumor-associated macrophages

Yoshitaka Ohno; Maiko Toshino; Ahmed F A Mohammed; Yukio Fujiwara; Yoshihiro Komohara; Risako Onodera; Taishi Higashi; Keiichi Motoyama

doi:10.1016/j.carbpol.2023.120551

Mannose-methyl-β-cyclodextrin suppresses tumor growth by targeting both colon cancer cells and tumor-associated macrophages

Carbohydr Polym. 2023 Apr 1:305:120551. doi: 10.1016/j.carbpol.2023.120551. Epub 2023 Jan 7.

Authors

Yoshitaka Ohno¹, Maiko Toshino², Ahmed F A Mohammed³, Yukio Fujiwara⁴, Yoshihiro Komohara⁴, Risako Onodera², Taishi Higashi⁵, Keiichi Motoyama⁶

Affiliations

¹ Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan; Program for Leading Graduate Schools "HIGO (Health Life Science: Interdisciplinary and Glocal Oriented) Program", Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan; Cross-disciplinary Doctoral Human Resource Development Program to Lead the Well-being Society, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
² Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
³ Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan; Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia, Egypt.
⁴ Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-0811, Japan.
⁵ Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan; Priority Organization for Innovation and Excellence, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.
⁶ Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan. Electronic address: motoyama@kumamoto-u.ac.jp.

PMID: 36737200
DOI: 10.1016/j.carbpol.2023.120551

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.

Keywords: Antitumor drug; Autophagy; Colorectal cancer; Cyclodextrin; Mannose.

MeSH terms

Animals
Colonic Neoplasms* / drug therapy
Mannose
Mice
Phosphatidylinositol 3-Kinases / metabolism
Tumor-Associated Macrophages
beta-Cyclodextrins* / pharmacology
beta-Cyclodextrins* / therapeutic use

Substances

methyl-beta-cyclodextrin
Mannose
Phosphatidylinositol 3-Kinases
beta-Cyclodextrins