2-Hydroxypropyl-β-Cyclodextrin Acts as a Novel Anticancer Agent
2-Hydroxypropyl-β-cyclodextrin (HP-β-CyD) is a cyclic oligosaccharide that is widely used as an enabling excipient in pharmaceutical formulations, but also as a cholesterol modifier. HP-β-CyD has recently been approved for the treatment of Niemann-Pick Type C disease, a lysosomal lipid storage disor...
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| Format: | Online |
| Language: | English |
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Public Library of Science
2015
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4633159/ |
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pubmed-4633159 |
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oai_dc |
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pubmed-46331592015-11-13 2-Hydroxypropyl-β-Cyclodextrin Acts as a Novel Anticancer Agent 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 Research Article 2-Hydroxypropyl-β-cyclodextrin (HP-β-CyD) is a cyclic oligosaccharide that is widely used as an enabling excipient in pharmaceutical formulations, but also as a cholesterol modifier. HP-β-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-β-CyD itself might have anticancer effects. This study provides evidence that HP-β-CyD inhibits leukemic cell proliferation at physiologically available doses. First, we identified the potency of HP-β-CyD in vitro against various leukemic cell lines derived from acute myeloid leukemia (AML), acute lymphoblastic leukemia and chronic myeloid leukemia (CML). HP-β-CyD treatment reduced intracellular cholesterol resulting in significant leukemic cell growth inhibition through G2/M cell-cycle arrest and apoptosis. Intraperitoneal injection of HP-β-CyD significantly improved survival in leukemia mouse models. Importantly, HP-β-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-β-CyD. Systemic administration of HP-β-CyD to mice had no significant adverse effects. These data suggest that HP-β-CyD is a promising anticancer agent regardless of disease or cellular characteristics. Public Library of Science 2015-11-04 /pmc/articles/PMC4633159/ /pubmed/26535909 http://dx.doi.org/10.1371/journal.pone.0141946 Text en © 2015 Yokoo et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
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 |
| spellingShingle |
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 2-Hydroxypropyl-β-Cyclodextrin Acts as a Novel Anticancer Agent |
| author_facet |
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 |
| author_sort |
Yokoo, Masako |
| title |
2-Hydroxypropyl-β-Cyclodextrin Acts as a Novel Anticancer Agent |
| title_short |
2-Hydroxypropyl-β-Cyclodextrin Acts as a Novel Anticancer Agent |
| title_full |
2-Hydroxypropyl-β-Cyclodextrin Acts as a Novel Anticancer Agent |
| title_fullStr |
2-Hydroxypropyl-β-Cyclodextrin Acts as a Novel Anticancer Agent |
| title_full_unstemmed |
2-Hydroxypropyl-β-Cyclodextrin Acts as a Novel Anticancer Agent |
| title_sort |
2-hydroxypropyl-β-cyclodextrin acts as a novel anticancer agent |
| description |
2-Hydroxypropyl-β-cyclodextrin (HP-β-CyD) is a cyclic oligosaccharide that is widely used as an enabling excipient in pharmaceutical formulations, but also as a cholesterol modifier. HP-β-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-β-CyD itself might have anticancer effects. This study provides evidence that HP-β-CyD inhibits leukemic cell proliferation at physiologically available doses. First, we identified the potency of HP-β-CyD in vitro against various leukemic cell lines derived from acute myeloid leukemia (AML), acute lymphoblastic leukemia and chronic myeloid leukemia (CML). HP-β-CyD treatment reduced intracellular cholesterol resulting in significant leukemic cell growth inhibition through G2/M cell-cycle arrest and apoptosis. Intraperitoneal injection of HP-β-CyD significantly improved survival in leukemia mouse models. Importantly, HP-β-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-β-CyD. Systemic administration of HP-β-CyD to mice had no significant adverse effects. These data suggest that HP-β-CyD is a promising anticancer agent regardless of disease or cellular characteristics. |
| publisher |
Public Library of Science |
| publishDate |
2015 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4633159/ |
| _version_ |
1613497448880144384 |