title: Release of cyclic phosphatidic acid from gelatin-based hydrogels inhibit colon cancer cell growth and migration.
abstract: Microparticle and nanoparticle formulations are widely used to improve the bioavailability of low-solubility drugs and as vehicles for organ- and tissue-specific targeted drug delivery. We investigated the effect of a novel, controlled-release form of a bioactive lipid, cyclic phosphatidic acid (cPA), on human colon cancer cell line functions. We encapsulated cPA in gelatin-based hydrogels and examined its ability to inhibit the viability and migration of HT-29 and DLD-1 cells in vitro and the LPA-induced activity of the transcription factor peroxisome proliferator-activated receptor gamma (PPARγ). The hydrogel delivery system prolonged cPA release into the culture medium. Accordingly, cPA-hydrogel microspheres substantially inhibited LPA-induced PPARγ activity and cell growth and migration compared with that of cells cultured with cPA alone. Thus, hydrogel microspheres are a potential system for stable and efficient delivery of bioactive lipids such as cPA and may offer a new strategy for targeted colon cancer treatment.
authors.affiliation: Department of Integrative Physiology & Bio-System Control, Shinshu University School of Medicine , 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan. ttamotsu@shinshuu.ac.jp
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Tsukahara
authors.forename: Kimiko
authors.initials: K
authors.lastname: Murakami-Murofushi
mesh_terms: D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000188:drug therapy; D016503:Drug Delivery Systems; D005780:Gelatin / Q000737:chemistry / Q000494:pharmacology; D019073:HT29 Cells; D006801:Humans; D020100:Hydrogels / Q000737:chemistry / Q000494:pharmacology; D008246:Lysophospholipids; D008863:Microspheres; D053758:Nanoparticles / Q000737:chemistry; D047495:PPAR gamma / Q000737:chemistry / Q000235:genetics; D010712:Phosphatidic Acids / Q000737:chemistry / Q000494:pharmacology
chemical_list: D020100:Hydrogels; D008246:Lysophospholipids; D047495:PPAR gamma; D010712:Phosphatidic Acids; D005780:Gelatin; C032881:lysophosphatidic acid