A novel PP2A enhancer induces caspase-independent apoptosis of MKN28 gastric cancer cells with high MEK activity

作者:Tsuchiya Ayako; Kanno Takeshi; Shimizu Tadashi; Nakao Syuhei; Tanaka Akito; Tabata Chiharu; Nakano Takashi; Nishizaki Tomoyuki*
来源:Cancer Letters, 2014, 347(1): 123-128.
DOI:10.1016/j.canlet.2014.01.034

摘要

The newly synthesized phosphatidylinositol (PI) derivative 1,2-0-bis-[8-{2-(2-pentyl-cyclopropylmethyl)-cyclopropyl)-octanoyl]-sn-glycero-3-phosphatidyl-D-1-inositol (diDCP-LA-PI) significantly enhanced protein phosphatase 2A (PP2A) activity in the cell-free assay. This prompted to assess the antitumor effect of diDCP-LA-PI. diDCP-LA-PI attenuated phosphorylation of mitogen-activated protein kinase (MAPK) kinase (MEK) in Lu65 human lung cancer and MKN28 human gastric cancer cells with high MEK activity. diDCP-LA-PI reduced cell viability in Lu65 and MKN28 cells, but otherwise such effect was not found in 786-O human renal cancer and HUH-7 human hepatoma cells with relatively low MEK activity. For Lu65 and MKN28 cells diDCP-LA-PI increased terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive cells, but no significant activation of caspase-3, -8, or -9 was obtained. For MKN28 cells diDCP-LA-PI-induced reduction of MEK phosphorylation and cell viability was prevented by knocking-down PP2Ac. Taken together, these results indicate that diDCP-LA-PI induces caspase-independent apoptosis of Lu65 and MKN28 human cancer cells, for the latter cells by suppressing MEK activity through PP2A-catalyzed dephosphorylation.

  • 出版日期2014-5-28