Figure 10.

A schematic diagram showing the possible relationship between apoptosis in Glioblastoma cells and the NKA-Src-JNK pathway. The connection of POH to the NKA-Src complex in the signalosome leads to the activation of JNK. Src inhibition (by dasatinib) and caveolae disruption (by methyl β-cyclodextrin) blocked the phosphorylation of JNK. JNK activation can induce apoptosis through cleavage of caspase-3. JNK inhibition (by the JNK inhibitor V) decreased the induction of apoptosis. The JNK-mediated production of IL-8 in GBM cells has not been described in the literature but an increase in the release of IL-8 might favor tumor progression. The solid lines indicate the findings of this study, whereas the dashed line show the known molecular mechanisms. POH: Perillyl alcohol; NKA: Na/K-ATPase; Src: Src Kinase; JNK: c-Jun N-terminal Kinase; and IL-8: Interleukin 8.