Luteolin sensitizes Fas/FasL-induced apoptosis in HepG2 cells through inhibiting Akt Activation and promoting XIAP Degradation

Fas, an important cell surface protein of the TNF receptor superfamily that induces apoptosis through binding Fas ligand or anti-Fas antibodies. Unfortunately, not all Fas-expressing cells are sensitive to its stimulus. Therefore it is important to study the mechanisms that counteract the FasL-induced apoptotic process which are still poorly understood. Luteolin, an important flavonoid present in a variety of edible plants, exhibits a wide spectrum of pharmacologic properties such as anticancer, antioxidant, and anti-inflammatory. Furthermore, much more attention has been turned to the chemosensitizing effect of luteolin on cancer cells death. In this study, we found that luteolin synergistically caused the FasL-induced apoptosis in HepG2 cells. Such potentiation was achieved through inhibiting Akt activation and promoting proteasomal degradation of X-linked Inhibitor of Apoptosis Protein (XIAP) which mediated the survival signals and allow the cells to escape from apoptosis in various human cancers.