RT Journal Article ID 732c959544c0f58a A1 Tanaka, Hiromasa A1 Mizuno, Masaaki A1 Ishikawa, Kenji A1 Nakamura, Kae A1 Utsumi, Fumi A1 Kajiyama, Hiroaki A1 Kano, Hiroyuki A1 Maruyama, Shoichi A1 Kikkawa, Fumitaka A1 Hori, Masaru T1 Cell survival and proliferation signaling pathways are downregulated by plasma-activated medium in glioblastoma brain tumor cells JF Plasma Medicine JO PMED YR 2012 FD 2014-07-22 VO 2 IS 4 SP 207 OP 220 K1 plasma-activated medium; glioblastoma; AKT; ERK; mTOR AB We previously reported that plasma-activated medium (PAM) selectively kills glioblastoma brain tumor cells by downregulating the signaling molecule, the serine-threonine kinase AKT. AKT kinase plays a key role in survival and proliferation by acting as a hub molecule in the signaling network to inhibit apoptosis. The pathways that contain AKT and that are affected by PAM are unclear. In this study of glioblastoma brain tumor cells, phosphorylation of AKT at both Ser473 and Thr308 was downregulated by PAM, suggesting that upstream signaling by the mammalian target of rapamycin complex 2 (mTORC2) and phosphatidylinositol- 3 kinase (PI3K)/ 3-phosphoinositide-dependent protein kinase-1 (PDK1) were affected by PAM. Furthermore, the extracellular regulated kinase (ERK) signaling pathway, which is parallel to the AKT signaling pathway, was downregulated by PAM, and the mTORC1 signaling pathway, which is a major downstream signaling pathway of AKT and ERK, was also downregulated by PAM. In addition, CD44, a cell membrane-bound receptor that promotes both the AKT pathway and the ERK pathway, was downregulated by PAM. Taken together, these results suggest that PAM completely downregulates the survival and proliferation signaling network in glioblastoma brain tumor cells. PB Begell House LK https://www.dl.begellhouse.com/journals/5a5b4a3d419387fb,25266a5313ab0f35,732c959544c0f58a.html