Dodo Kosuke, Sato Ayato, Tamura Yuki, Egoshi Syusuke, Fujiwara Koichi, Oonuma Kana, Nakao Shuhei, Terayama Naoki, Sodeoka Mikiko
Synthetic Organic Chemistry Laboratory, RIKEN Cluster for Pioneering Research, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
Chem Commun (Camb). 2021 Mar 1;57(17):2180-2183. doi: 10.1039/d0cc07824g.
γ-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.
据报道，γ-亚麻酸（GLA）通过不明机制表现出肿瘤选择性细胞毒性。在此，为评估GLA氧化代谢产物的作用，我们合成了几种氘代GLA，并评估了它们的代谢情况以及对正常人成纤维细胞WI-38细胞和通过用SV40病毒转化WI-38细胞产生的VA-13肿瘤细胞的细胞毒性。GLA的氘代抑制了对WI-38细胞的代谢和细胞毒性，并增加了对VA-13细胞的选择性。通过拉曼成像观察到完全氘代的GLA，这表明GLA积聚在VA-13细胞的细胞内脂滴中。我们的结果表明，肿瘤选择性细胞毒性是由于GLA本身，而非其氧化代谢产物。
