Melatonin: The smart killer: The human trophoblast as a model

Melatonin has both the ability to induce intrinsic apoptosis in tumor cells while it inhibits it in non-tumor cells. Melatonin kills tumor cells through induction of reactive oxygen species generation and activation of pro-apoptotic pathways. In contrast, melatonin promotes the survival of non-tumor cells due to its antioxidant properties and the inhibition of pro-apoptotic pathways. In primary human villous trophoblast, a known pseudo-tumorigenic tissue, melatonin promotes the survival through inhibition of the Bax/Bcl-2 pathway while in BeWo choriocarcinoma cell line melatonin induces permeabilization of the mitochondrial membrane leading to cellular death. These findings suggest that the trophoblast is a good model to study the differential effects of melatonin on the intrinsic apoptosis pathway. This review describes the differential effects of melatonin on the intrinsic apoptosis pathway in tumor and non-tumor cells and presents the trophoblast as a novel model system in which to study these effects of melatonin.

► Melatonin activates the pro-apoptotic pathways in tumor cells. ► Melatonin inhibits the pro-apoptotic pathways in non-tumor cells. ► Melatonin has dual effects on intrinsic apoptosis in normal and tumoral trophoblast. ► Melatonin has therapeutic potential in cancer. ► Primary human placental trophoblast cells are an excellent pseudo-tumorigenic model.