Kosuke Dodo, Ayato Sato, Yuki Tamura, Syusuke Egoshi, Koichi Fujiwara, Kana Oonuma, Shuhei Nakao, Naoki Terayama, Mikiko Sodeoka (2021) Synthesis of deuterated gamma-linolenic acid and application for biological studies: metabolic tuning and Raman imaging., Chemical communications (Cambridge, England), Volume 57, Number 17, pp. 2180-2183
Published in 2021 Mar 1
(Abstract) gamma-Linolenic acid (GLA) is reported to show tumor-selective cytotoxicity through unidentified mechanisms. Here, to assess the involvement of oxidized metabolites of GLA, we synthesized several deuterated GLAs and evaluated their metabolism and cytotoxicity towards normal human fibroblast WI-38 cells and VA-13 tumor cells generated from WI-38 by transformation with SV40 virus. Deuteration of GLA suppressed both metabolism and cytotoxicity towards WI-38 cells and increased the selectivity for VA-13 cells. Fully deuterated GLA was visualized by Raman imaging, which indicated that GLA is accumulated in intracellular lipid droplets of VA-13 cells. Our results suggest the tumor-selective cytotoxicity is due to GLA itself, not its oxidized metabolites.(MeSH Terms)