Photochemotherapy using natural anthraquinones: rubiadin and soranjidiol sensitize human cancer cell to die by apoptosis

NATALIA BELEN RUMIE VITTAR; LAURA COMINI; IVANA MARIA FERNADEZ; ELIZABETH AGOSTINI; SUSANANUNEZ-MONTOYA; JOSE LUIS CABRERA; VIVIANA ALICIA RIVAROLA

Photodiagnosis Photodynamic Therapy

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2014

1572-1000

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  u-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.