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Published on: June 18, 2015
Mannose-methyl-β-cyclodextrin suppresses tumor growth by targeting both colon cancer cells and tumor-associated
Yoshitaka Ohno1, Maiko Toshino2, Ahmed F A Mohammed3
1Graduate 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.
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.
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