Swainsonine induces caprine luteal cells apoptosis via mitochondrial-mediated caspase-dependent pathway

Swainsonine (SW) is an indolizidine alkaloid isolated from a number of poisonous plants. We have previously reported that SW inhibited luteal cell progesterone production by inducing caprine luteal cell apoptosis in vitro; however, the molecular mechanism of this phenomenon remains unclear. In this study, SW-treated luteal cells showed apoptosis characteristics, including nuclear fragmentation, DNA ladder formation, and phosphatidylserine externalization. Further studies showed that SW activated caspase-9 and caspase-3, which subsequently cleaved poly(ADP-ribose) polymerase. SW also increased in Bax/BcL-2 ratios, promoted Bax translocation from the cytosol to mitochondria, and triggered the release of cytochrome c from mitochondria into the cytoplasm. However, Fas and Fas ligand induction or caspase-8 activity did not appear any significant changes. Additional analysis also showed that pan-caspase inhibitor, caspase-9 inhibitor, or caspase-3 inhibitor almost completely protected the cells from SW-induced apoptosis, but not caspase-8 inhibitor. Overall, these data demonstrated that SW induced luteal cells apoptosis through a mitochondrial-mediated caspase-dependent pathway.