title: Isolation of hypoxia-inducible factor 1 (HIF-1) inhibitors from frankincense using a molecularly imprinted polymer.
abstract: Hypoxia-Inducible Factor 1 (HIF-1), a transcriptional activator, is highly involved in the pathology of cancer. Inhibition of HIF-1 retards tumor growth and enhances treatment efficiency when used in combination with chemo- or radiation therapy. The recent validation of HIF-1 as an important drug target in cancer treatment has stimulated efforts to identify and isolate natural or synthetic HIF-1 inhibitors. In the present study, quercetin, a known inhibitor of HIF-1, was imprinted in a polymer matrix in order to prepare a Molecularly Imprinted Polymer (MIP), which was subsequently used for the selective isolation of new inhibitors from frankincense, a gum resin used as anticancer remedy in traditional medicine. The frankincense components isolated by Solid Phase Extraction on MIP (MIP-SPE), efficiently inhibited the transcriptional activity of HIF-1 and decreased the protein levels of HIF-1α, the regulated subunit of HIF-1. The selective retention of acetyl 11-ketoboswellic acid (AKBA, one of the main bioactive components of frankincense) by MIP led to the revealing of its inhibitory activity on the HIF-1 signaling pathway. AKBA was selectively retained by SPE on the quercetin imprinted polymer, with an imprinting effect of 8.1 ± 4.6. Overall, this study demonstrates the potential of MIP application in the screening, recognition and isolation of new bioactive compounds that aim selected molecular targets, a potential that has been poorly appreciated until.
authors.affiliation: Department of Biochemistry, School of Medicine, Faculty of Life Sciences, University of Thessaly, 41110 Biopolis, Larissa, Greece.
authors.forename: Achillia
authors.initials: A
authors.lastname: Lakka
authors.forename: Ilias
authors.initials: I
authors.lastname: Mylonis
authors.forename: Sophia
authors.initials: S
authors.lastname: Bonanou
authors.forename: George
authors.initials: G
authors.lastname: Simos
authors.forename: Andreas
authors.initials: A
authors.lastname: Tsakalof
mesh_terms: D000970:Antineoplastic Agents / Q000302:isolation & purification* / Q000494:pharmacology*; D029743:Boswellia / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors* / Q000235:genetics; D054802:Molecular Imprinting / Q000379:methods*; D011108:Polymers / Q000737:chemistry*; D011794:Quercetin / Q000737:chemistry*; D052616:Solid Phase Extraction; D014158:Transcription, Genetic / Q000187:drug effects; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D011108:Polymers; D014315:Triterpenes; C054625:boswellic acid; D011794:Quercetin