abscisic-acid and Glioblastoma

As a widely known plant hormone, Abscisic acid plays an important role in the progress of planting cell and their stress response. Recently, we reported that ABA might play an anti-cancer role in glioma tissues. In the present study, the molecular mechanism of ABA anti-cancer was further explored in glioblastoma cells. By measuring LC3 puncta formation and conversion in glioblastoma cells, inhibiting the autophagic pathway, targeting the essential autophagic modulator beclin 1 with RNA interference, and analysing cellular morphology via transmission electron microscopy, we found that ABA-treated glioblastoma cells exhibited the features of autophagy. Specifically, ABA-induced autophagy in glioblastoma cells was mediated by the MAPK/JNK signalling pathway rather than the PI3K/AKT/mTOR axis. Moreover, the inhibition or knockdown of JNK specifically blocked ABA-induced autophagic cell death. ABA-induced autophagy was further confirmed in tumour-bearing mice and was accompanied by the inhibition of glioma growth in vivo. This report is the first to describe autophagy induced by ABA and mediated by the MAPK/JNK pathway in human cancer cells and tumour-bearing mice. These results may shed some light in new therapeutic strategies of glioma.

Topics: Abscisic Acid; Allografts; Animals; Autophagosomes; Autophagy; Beclin-1; Cell Line, Tumor; Cell Proliferation; Down-Regulation; Glioblastoma; Humans; MAP Kinase Signaling System; Mice, Inbred BALB C; Mice, Nude; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; TOR Serine-Threonine Kinases; Vacuoles