Effects of 6-O-α-maltosyl-γ cyclodextrin on proliferation and cellular uptake in mouse mastocytoma P-815 cells

6-O-α-Maltosyl-γ cyclodextrin (Mal-γCD) is a branched γCD with α(1 → 6) branched maltose on the γCD ring. Mal-γCD is more water-soluble and safer than the parent γCD, has the same ability to form inclusion complexes, and the formed inclusion complexes are highly water-soluble. There is limited information regarding Mal-γCD both in vitro and in vivo, and the effects of Mal-γCD on proliferation, uptake, metabolism, and the cell cycle of target cells remain unknown. In this study, we investigated the effects of Mal-γCD on the proliferation of mastocytoma P-815 cells (P-815 cells) focusing on its impact on the cellular uptake, endocytosis, metabolism, and the cell cycle. We found that Mal-γCD, but not the parent γCD, inhibited the proliferation of P-815 cells in a time- and concentration-dependent manner, although the inhibition was reversible. Mal-γCD caused an increase in the number of cells in the G1 and G2 phases and a decrease in the number of cells in the S phase. Mal-γCD was taken up by P-815 cells and metabolized to 6-O-α-d-glucosyl-γCD and glucose by cellular α-glucosidases in a time-dependent manner. Its uptake was enhanced in S-phase-synchronized P-815 cells, was temperature- and energy-dependent, and was suppressed by general endocytosis inhibitors such as cytochalasin D and colchicine, as well as by Na⁺/K⁺-ATPase inhibitors such as digoxin, quinidine, and verapamil. These findings demonstrate that Mal-γCD exerts a growth inhibitory effect on proliferative cells by delaying the cell cycle at the G1/S and G2/M transition phases, which may be closely associated with endocytosis.