Antitumor effect of liposomal histone deacetylase inhibitor-lipid conjugates in vitro
Related Experiment Video
Updated: May 28, 2026
Simultaneous Measurement of HDAC1 and HDAC6 Activity in HeLa Cells Using UHPLC-MS
Published on: August 10, 2017
Yoshiyuki Hattori1, Yasuo Nagaoka, Manami Kubo
1Institute of Medicinal Chemistry, Hoshi University, Tokyo 142–8501, Japan. yhattori@hoshi.ac.jp
Abstract:
Histone deacetylase inhibitor (HDACI), suberoylanilide hydroxamic acid (SAHA), approved by the Food and Drug Administration (FDA) for the treatment of cutaneous T cell lymphoma, is a promising new treatment strategy for various cancers. In this study, we hypothesized that a liposomal formulation of HDACI might efficiently deliver HDACI into tumors. To incorporate HDACI efficiently into the liposomal membrane, we synthesized six HDACI-lipid conjugates, in which polyethylene glycol(2000) (PEG(2000))-lipid or cholesterol (Chol) was linked with a potent hydroxamic acid, HDACI, SAHA or K-182, by cleavable linkers, such as ester, carbamide and disulfide bonds. Liposomal HDACI-lipid conjugates were prepared with distearoylphosphatidylcholine (DSPC) and HDACI-Chol conjugate or with DSPC, Chol and HDACI-PEG-lipid conjugates, and their cytotoxicities were evaluated for human cervix tumor HeLa and mouse colon tumor Colon 26 cells. Among the liposomes, liposomal oleyl-PEG(2000)-SAHA conjugated with SAHA and oleyl-PEG(2000) via a carbamate linker showed higher cytotoxicity via hyperacetylation of histone H3 and induction of caspase 3/7 activity. These results suggested that liposomal HDACI-lipid conjugates may be a potential tool for cancer therapy.
Insights
Liposomal formulations of histone deacetylase inhibitors (HDACI) show potential for cancer therapy. A novel liposomal SAHA conjugate demonstrated enhanced cytotoxicity in cancer cells, suggesting a promising delivery strategy.
Area of Science:
- Oncology
- Nanomedicine
- Drug Delivery
Background:
- Histone deacetylase inhibitors (HDACI), such as suberoylanilide hydroxamic acid (SAHA), are FDA-approved for cutaneous T cell lymphoma and show promise for other cancers.
- Efficient delivery of HDACI into tumor cells remains a challenge for effective cancer therapy.
Purpose of the Study:
- To develop and evaluate liposomal formulations of HDACI for improved tumor targeting and efficacy.
- To synthesize novel HDACI-lipid conjugates for incorporation into liposomes.
Main Methods:
- Six HDACI-lipid conjugates were synthesized, linking HDACI (SAHA or K-182) to polyethylene glycol(2000)-lipid or cholesterol via cleavable linkers (ester, carbamide, disulfide).
- Liposomes were prepared using distearoylphosphatidylcholine (DSPC) and either HDACI-cholesterol conjugates or HDACI-PEG-lipid conjugates.
- Cytotoxicity of liposomal formulations was assessed against human cervix tumor HeLa and mouse colon tumor Colon 26 cells.
Main Results:
- Liposomal oleyl-PEG(2000)-SAHA, utilizing a carbamate linker, exhibited superior cytotoxicity compared to other formulations.
- Enhanced cytotoxicity was attributed to histone H3 hyperacetylation and caspase 3/7 activity induction.
- The study identified a specific liposomal HDACI-lipid conjugate with significant anti-cancer potential.
Conclusions:
- Liposomal HDACI-lipid conjugates represent a promising strategy for targeted cancer therapy.
- The developed liposomal SAHA formulation demonstrates enhanced anti-cancer activity, supporting its potential clinical application.
- Further research into liposomal drug delivery systems for HDACI is warranted for various oncological indications.
