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2-Hydroxypropyl-[beta]-Cyclodextrin Acts as a Novel Anticancer Agent

2-Hydroxypropyl-[beta]-cyclodextrin (HP-[beta]-CyD) is a cyclic oligosaccharide that is widely used as an enabling excipient in pharmaceutical formulations, but also as a cholesterol modifier. HP-[beta]-CyD has recently been approved for the treatment of Niemann-Pick Type C disease, a lysosomal lipi...

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Bibliographic Details
Published in:PloS one 2015-11, Vol.10 (11)
Main Authors: Yokoo, Masako, Kubota, Yasushi, Motoyama, Keiichi, Higashi, Taishi, Taniyoshi, Masatoshi, Tokumaru, Hiroko, Nishiyama, Rena, Tabe, Yoko, Mochinaga, Sakiko, Sato, Akemi, Sueoka-Aragane, Naoko, Sueoka, Eisaburo, Arima, Hidetoshi, Irie, Tetsumi, Kimura, Shinya
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Language:English
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Summary:2-Hydroxypropyl-[beta]-cyclodextrin (HP-[beta]-CyD) is a cyclic oligosaccharide that is widely used as an enabling excipient in pharmaceutical formulations, but also as a cholesterol modifier. HP-[beta]-CyD has recently been approved for the treatment of Niemann-Pick Type C disease, a lysosomal lipid storage disorder, and is used in clinical practice. Since cholesterol accumulation and/or dysregulated cholesterol metabolism has been described in various malignancies, including leukemia, we hypothesized that HP-[beta]-CyD itself might have anticancer effects. This study provides evidence that HP-[beta]-CyD inhibits leukemic cell proliferation at physiologically available doses. First, we identified the potency of HP-[beta]-CyD in vitro against various leukemic cell lines derived from acute myeloid leukemia (AML), acute lymphoblastic leukemia and chronic myeloid leukemia (CML). HP-[beta]-CyD treatment reduced intracellular cholesterol resulting in significant leukemic cell growth inhibition through G.sub.2 /M cell-cycle arrest and apoptosis. Intraperitoneal injection of HP-[beta]-CyD significantly improved survival in leukemia mouse models. Importantly, HP-[beta]-CyD also showed anticancer effects against CML cells expressing a T315I BCR-ABL mutation (that confers resistance to most ABL tyrosine kinase inhibitors), and hypoxia-adapted CML cells that have characteristics of leukemic stem cells. In addition, colony forming ability of human primary AML and CML cells was inhibited by HP-[beta]-CyD. Systemic administration of HP-[beta]-CyD to mice had no significant adverse effects. These data suggest that HP-[beta]-CyD is a promising anticancer agent regardless of disease or cellular characteristics.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0141946