Fig. 2. Apoptosis pathways and the points targeted by luteolin.

The extrinsic apoptosis pathway is mediated by death receptors, resulting in sequential activation of initiator caspase 8 and executor caspases 3 and 7. The intrinsic apoptosis pathway is initiated by lose of mitochondrial potential, which leads to release of cytochrome c. Cytochrome c binds to APAF-1 and procaspase 9, resulting in activation of initiator caspase 9 and downstream executor caspases. Cleavage of Bid by caspase 8 establishes a crosstalk between the extrinsic and intrinsic apoptosis pathways. Luteolin triggers apoptotic cell death through potentiation of both apoptosis pathways and suppression of cell survival pathways. The points targeted by luteolin in the apoptosis pathways are highlighted with numbers in filled circles.