%0 Journal Article
%T Polyunsaturated fatty acids synergize with lipid droplet binding thalidomide analogs to induce oxidative stress in cancer cells
%A L¨˘szl¨® G Pusk¨˘s
%A Lili¨˘na Z Feh¨¦r
%A Csaba Vizler
%A Ferhan Ayaydin
%A Erzs¨¦bet R¨˘s¨®
%A Eszter Moln¨˘r
%A Istv¨˘n Magyary
%A Iv¨˘n Kanizsai
%A M¨˘ri¨® Gyuris
%A Ram¨®na Mad¨˘csi
%A Gabriella F¨˘bi¨˘n
%A Klaudia Farkas
%A P¨¦ter Hegyi
%A Ferenc Baska
%A B¨¦la ¨®zsv¨˘ri
%A Kl¨˘ra Kitajka
%J Lipids in Health and Disease
%D 2010
%I BioMed Central
%R 10.1186/1476-511x-9-56
%X Cytotoxicity was detected in different cell lines including melanoma, leukemia, hepatocellular carcinoma, glioblastoma at micromolar concentrations. The synthesized analogs are non-toxic to adult animals up to 1 g/kg but are teratogenic to zebrafish embryos at micromolar concentrations with defects in the developing muscle. Treatment of tumor cells resulted in calcium release from the endoplasmic reticulum (ER), induction of reactive oxygen species (ROS), ER stress and cell death. Antioxidants could partially, while an intracellular calcium chelator almost completely diminish ROS production. Exogenous docosahexaenoic acid or eicosapentaenoic acid induced calcium release and ROS generation, and synergized with the analogs in vitro, while oleic acid had no such an effect. Gene expression analysis confirmed the induction of ER stress-mediated apoptosis pathway components, such as GADD153, ATF3, Luman/CREB3 and the ER-associated degradation-related HERPUD1 genes. Tumor suppressors, P53, LATS2 and ING3 were also up-regulated in various cell lines after drug treatment. Amino-phthalimides down-regulated the expression of CCL2, which is implicated in tumor metastasis and angiogenesis.Because of the anticancer, anti-angiogenic action and the wide range of applicability of the immunomodulatory drugs, including thalidomide analogs, lipid droplet-binding members of this family could represent a new class of agents by affecting ER-membrane integrity and perturbations of ER homeostasis.Cytoplasmic lipid-droplets (LDs) are common inclusions of eukaryotic cells. Little is known about the composition or physiological role of LDs, however growing number of evidences imply that LDs are not solely static inclusions for storage of excess lipid, but they are dynamic and functionally active [1-4]. Although LD biogenesis is not well understood, it is assumed that the LDs form within the two leaflets of the ER membrane to function as lipid storage sites [5]. LDs are active inclusions with e
%U http://www.lipidworld.com/content/9/1/56