Melanoma response mechanisms to hypericin-PDT.

<p>Hypericin (HYP) was taken up by melanoma cells and localized to various intracellular organelles, including the endoplasmic reticulum, mitochondria, lysosomes and melanosomes. Light activation (yellow arrow) of hypericin, in the presence of oxygen (O₂), resulted in loss of structural details of various intracellular organelles, phosphatidylserine (PS) exposure, loss of melanoma cell membrane integrity, cell shrinkage and an increase in granularity/pigmentation. Hypericin-PDT furthermore initiated caspase-dependent apoptotic modes of cell death of both extrinsic (caspase 8 (CASP8)) and intrinsic (caspase 3 (CASP3)) nature, as well as a caspase-independent apoptotic mode that did not involve apoptosis inducing factor (AIF). Both caspase-dependent and caspase-independent apoptotic modes of cell death resulted in the cleavage of poly(ADP-ribose)polymerase 1 (PARP1).