Fig. 9

Schematic representation of curcuminoid analogues (FLDP-5 and FLDP-8)-induced apoptosis in LN-18 human GBM cells. The FLDP-5 and FLDP-8 curcuminoid analogues induce apoptosis in LN-18 cells via both intrinsic and extrinsic pathways. Through the cleavage of pro-caspase-8, both analogues induce an extrinsic apoptotic pathway. The active caspase-8 then cleaves the downstream effector pro-caspase-3 as well as the proapoptotic protein Bid, changing them to active forms. The resulting tBid then induces the release of mitochondrial proapoptotic components, potentially connecting the two pathways. The curcuminoid analogues FLDP-5 and FLDP-8 also induce the intrinsic apoptotic pathway. This pathway is activated by an early DNA damage that impacts the mitochondria, resulting in MMP and cardiolipin loss. This impact initiates the release of cytochrome c into the cytoplasm, ultimately forming an apoptosome with Apaf-1. This is followed by the cleavage of pro-caspase-9, which cleaves executor pro-caspase-3, the key player in the downstream events of apoptosis. Both curcuminoid analogues were also suggested to induce apoptosis by suppressing miRNA-21