Photochemotherapy using natural anthraquinones: Rubiadin and Soranjidiol sensitize human cancer cell to die by apoptosis

Abstract

Over the past decade the science has studied synthetic photosensitizers used in photodynamic therapy (PDT) or photochemotherapy as anticancer candidates. In this context, compounds extracted from vegetable species present interesting potential in the cancer field. In our laboratory, we studied Heterophyllaea pustulata a phototoxic shrub that habit the northwest of Argentina. From this vegetal, by in vitro germination, we obtained Rubiadin and Soranjidiol, two anthraquinones that exhibited significant photocytotoxicity on human cancer cells. In addition, the fraction obtained from callus cultures allowed us to get a satisfactory content of these compounds compared to those found from the original plant. Under PDT regimen, we found that cell destruction resulted in a dose-dependent manner and occasioned apoptosis on photosensitized cells. Biochemical analysis revealed the involvement of caspase-3, PARP cleavage and DNA fragmentation in Rubiadin induced apoptosis. Moreover, Soranjidiol-PDT led to μ-calpain-induced apoptosis involving caspases-3-independent DNA fragmentation. We also showed that both anthraquinones are cytoplasmatically distributed and out of nucleus. In addition, we demonstrated a synergic cytotoxic effect when we combined them. Our data demonstrated that Rubiadin and Soranjidiol could be further considered as natural photocytotoxic compounds against cancer cells and callus cultures are a plausible source of these anthraquinonic compounds.