Doxorubicin-mediated apoptosis in glioma cells requires NFAT3

S Gopinath, SK Vanamala, M Gujrati… - Cellular and molecular …, 2009 - Springer
S Gopinath, SK Vanamala, M Gujrati, JD Klopfenstein, DH Dinh, JS Rao
Cellular and molecular life sciences, 2009Springer
Nuclear factor of activated T cells (NFAT), a family of transcription factors, has been
implicated in many cellular processes, including some cancers. Here, we characterize, for
the first time, the role of NFAT3 in doxorubicin (DOX)-mediated apoptosis, migration, and
invasion in SNB19 and U87 glioma cells. This study demonstrates that the specific
knockdown of NFAT3 results in a dramatic inhibition of the apoptotic effect induced by DOX
and favors cell survival. Inhibition of NFAT3 activation by shNFAT3 (shNF3) significantly …
Abstract
Nuclear factor of activated T cells (NFAT), a family of transcription factors, has been implicated in many cellular processes, including some cancers. Here, we characterize, for the first time, the role of NFAT3 in doxorubicin (DOX)-mediated apoptosis, migration, and invasion in SNB19 and U87 glioma cells. This study demonstrates that the specific knockdown of NFAT3 results in a dramatic inhibition of the apoptotic effect induced by DOX and favors cell survival. Inhibition of NFAT3 activation by shNFAT3 (shNF3) significantly downregulated tumor necrosis factor (TNF)-α induction, its receptor TNFR1, caspase 10, caspase 3, and poly (ADP-ribose) polymerase, abrogating DOX-mediated apoptosis in glioma cells. DOX treatment resulted in NFAT3 translocation to the nucleus. Similarly, shNF3 treatment in SNB19 and U87 cells reversed DOX-induced inhibition of cell migration and invasion, as determined by wound healing and matrigel invasion assays. Taken together, these results indicate that NFAT3 is a prerequisite for the induction of DOX-mediated apoptosis in glioma cells.
Springer