title: Synthesis of Vorinostat and cholesterol conjugate to enhance the cancer cell uptake selectivity.
abstract: Histone deacetylase (HDAC) inhibitors modulate various cellular functions including proliferation, differentiation, and apoptosis. Vorinostat (SuberAniloHydroxamic Acid, SAHA) is the first HDAC inhibitor approved by FDA for cancer treatment. However, SAHA distributes in cancer tissue and normal tissue in similar levels. It will be ideal to selectively deliver SAHA into cancer cells. Rapidly growing cancer cells have a great need of cholesterol. Low-density lipoprotein (LDL) is the major cholesterol carrier in plasma and its uptake is mediated by LDL-receptor (LDL-R), a glycoprotein overexpressed on the surface of cancer cells. Herein, we designed and synthesized a SAHA cholesterol conjugate, and further formed the conjugate containing particles with LDL as the carrier. The diameters of the particles were determined. The inhibitory activity of the particles carrying the conjugate was determined with cancer cell proliferation assay, and the hydrolysis of the conjugate by the enzymes in cancer cells was confirmed with LC-MS/MS.
authors.affiliation: Department of Chemistry, Center for Gene Regulation in Health and Disease, College of Sciences and Health Professions, Cleveland State University, 2121 Euclid Ave., Cleveland, OH 44115, USA.
authors.forename: Nethrie D
authors.initials: ND
authors.lastname: Idippily
authors.affiliation: College of Chemistry and Life Science, Key Laboratory of Beibu Gulf Environment Change and Resources Utilization, Guangxi Teachers Education University, Nanning 530001, China.
authors.forename: Chunfang
authors.initials: C
authors.lastname: Gan
authors.affiliation: Department of Chemistry, Center for Gene Regulation in Health and Disease, College of Sciences and Health Professions, Cleveland State University, 2121 Euclid Ave., Cleveland, OH 44115, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Orefice
authors.affiliation: Department of Chemistry, Center for Gene Regulation in Health and Disease, College of Sciences and Health Professions, Cleveland State University, 2121 Euclid Ave., Cleveland, OH 44115, USA.
authors.forename: Jane
authors.initials: J
authors.lastname: Peterson
authors.affiliation: Department of Chemistry, Center for Gene Regulation in Health and Disease, College of Sciences and Health Professions, Cleveland State University, 2121 Euclid Ave., Cleveland, OH 44115, USA. Electronic address: b.su@csuohio.edu.
authors.forename: Bin
authors.initials: B
authors.lastname: Su
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002784:Cholesterol / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D056572:Histone Deacetylase Inhibitors / Q000032:analysis / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D006877:Hydroxamic Acids / Q000737:chemistry*; D011973:Receptors, LDL / Q000378:metabolism; D053719:Tandem Mass Spectrometry; D000077337:Vorinostat
chemical_list: D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D011973:Receptors, LDL; D000077337:Vorinostat; D002784:Cholesterol
keywords: Cancer; Cholesterol; LDL-receptor; SAHA