Hypericin and
hypocrellin are potential
antiviral and
antineoplastic agents with multiple modes of light-induced
biological activity connected with a production of
singlet oxygen and/or excited-state
proton transfer and consequent pH drop formation in the drugs environment. In present work light-induced cytotoxicity of
hypericin and
hypocrellin and mechansim of cell death (apoptosis or
necrosis) on human leukemic cell line HL-60 was studied. As a mean for apoptosis detection we used
poly (ADP-ribose) polymerase (PARP) as a sensitive marker of early stages of apoptosis. Our results show that exposition of HL-60 cells to
hypericin (1 x 10(-5) mol x l(-1)) for 4 hours has no effect on PARP cleavage. However, after 24 and 48 hours of illumination there is evident that
hypericin in this concentration cleaved PARP (116 kDa) into two fragments (85 and 25 kDa). Contrary to
hypericin,
hypocrellin in concentration 1 x 10(-5) mol x l(-1) after 4 hours of illumination cleaved PARP into two fragments typical for apoptosis. In lower concentration (1 x 10(-6) mol x l(-1))
hypocrellin possess also significant cytotoxic activity. Because we detected no fragmentation of PARP in all observed time periods we suggest that cytotoxic effect of
hypocrellin in this concentration is due to induction of
necrosis. Our results support the hypotesis that the
hypericin and
hypocrellin has similar mechanism of action and illumination increases cytotoxic effect of both agents.