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Different modulation of TRAIL‐induced apoptosis by inhibition of pro‐survival pathways in TRAIL‐sensitive and TRAIL‐resistant colon cancer cells
Author(s) -
Vaculová Alena,
Hofmanová Jiřina,
Souček Karel,
Kozubík Alois
Publication year - 2006
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2006.11.004
Subject(s) - protein kinase b , apoptosis , pi3k/akt/mtor pathway , mapk/erk pathway , ly294002 , gsk 3 , cancer research , microbiology and biotechnology , chemistry , signal transduction , glycogen synthase , mek inhibitor , kinase , cancer cell , biology , cancer , phosphorylation , biochemistry , genetics
Epithelial cells can be manipulated to undergo apoptosis depending on the balance between pro‐survival and apoptotic signals. We showed that TRAIL‐induced apoptosis may be differentially regulated by inhibitors of MEK ERK (U0126) or PI3K/Akt (LY294002) pathway in TRAIL‐sensitive (HT‐29) and TRAIL‐resistant (SW620) human epithelial colon cancer cells. U0126 or LY294002 significantly enhanced TRAIL‐induced apoptosis in HT–29 cells, but not in SW620 cells. We report a different regulation of the level of an anti‐apoptotic Mcl‐1 protein under MEK/ERK or PI3K/Akt pathway inhibition and suggest the mechanisms involved. A special attention was paid to the role of the ERK1/2, Akt, and glycogen synthase kinase 3β.