title: A novel PP2A enhancer induces caspase-independent apoptosis of MKN28 gastric cancer cells with high MEK activity.
abstract: The newly synthesized phosphatidylinositol (PI) derivative 1,2-O-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.
authors: Division of Bioinformation, Department of Physiology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya 663-8501, Japan.
authors: Ayako
authors: A
authors: Tsuchiya
authors: Division of Bioinformation, Department of Physiology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya 663-8501, Japan.
authors: Takeshi
authors: T
authors: Kanno
authors: Laboratory of Chemical Biology, Advanced Medicinal Research Center, Hyogo University of Health Sciences, 1-3-6 Minatojima, Chuo-ku, Kobe 650-8530, Japan.
authors: Tadashi
authors: T
authors: Shimizu
authors: Laboratory of Chemical Biology, Advanced Medicinal Research Center, Hyogo University of Health Sciences, 1-3-6 Minatojima, Chuo-ku, Kobe 650-8530, Japan.
authors: Syuhei
authors: S
authors: Nakao
authors: Laboratory of Chemical Biology, Advanced Medicinal Research Center, Hyogo University of Health Sciences, 1-3-6 Minatojima, Chuo-ku, Kobe 650-8530, Japan.
authors: Akito
authors: A
authors: Tanaka
authors: Department of Thoracic Oncology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya 663-8501, Japan.
authors: Chiharu
authors: C
authors: Tabata
authors: Department of Thoracic Oncology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya 663-8501, Japan.
authors: Takashi
authors: T
authors: Nakano
authors: Division of Bioinformation, Department of Physiology, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya 663-8501, Japan. Electronic address: tomoyuki@hyo-med.ac.jp.
authors: Tomoyuki
authors: T
authors: Nishizaki
mesh_terms: D017209:Apoptosis; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor; D006801:Humans; D020287:In Situ Nick-End Labeling; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism*; D010766:Phosphorylation; D054648:Protein Phosphatase 2 / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000201:enzymology / Q000473:pathology*
chemical_list: D020930:MAP Kinase Kinase Kinases; D054648:Protein Phosphatase 2; D020169:Caspases
keywords: Cancer cell; Caspase-independent apoptosis; MEK; Phosphatidylinositol derivative; Protein phosphatase 2A