Potential use of folate-appended methyl-β-cyclodextrin as an anticancer agent.
To obtain a tumor cell-selectivity of methyl-β-cyclodextrin (M-β-CyD), we newly synthesized folate-appended M-β-CyD (FA-M-β-CyD), and evaluated the potential of FA-M-β-CyD as a novel anticancer agent in vitro and in vivo. Potent antitumor activity and cellular association of FA-M-β-CyD were higher than those of M-β-CyD in KB cells, folate receptor (FR)-positive cells. FA-M-β-CyD drastically inhibited the tumor growth after intratumoral or intravenous injection to FR-positive Colon-26 cells-bearing mice. The antitumor activity of FA-M-β-CyD was comparable and superior to that of doxorubicin after both intratumoral and intravenous administrations, respectively, at the same dose, in the tumor-bearing mice. All of the tumor-bearing mice after an intravenous injection of FA-M-β-CyD survived for at least more than 140 days. Importantly, an intravenous administration of FA-M-β-CyD to tumor-bearing mice did not show any significant change in blood chemistry values. These results strongly suggest that FA-M-β-CyD has the potential as a novel anticancer agent.
Graduate School of Pharmaceutical Sciences, Kumamoto University, Chuo-ku, Kumamoto 862-0973, Japan.
Risako
R
Onodera
Keiichi
K
Motoyama
Ayaka
A
Okamatsu
Taishi
T
Higashi
Hidetoshi
H
Arima
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000378:metabolism; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology; D005492:Folic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007624:KB Cells; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011817:Rabbits; D023041:Xenograft Model Antitumor Assays; D047392:beta-Cyclodextrins / Q000494:pharmacology*
D000970:Antineoplastic Agents; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; D004317:Doxorubicin; D005492:Folic Acid; D002784:Cholesterol; D053148:Caspase 3; D053179:Caspase 7