Photo-activation of hypericin with low doses of light promotes apparentphoto-resistance in human histiocytic lymphoma U937 cells

We have observed that exposure of U937 cells, pre-incubated for 18 h with 0.2 mM hypericin, to 599 nm laser radiation with a fluence 2 of 2.5 J /cm renders them insensitive to higher light doses. In fact, pre-sensitized cells appear to be fully resistant to light doses that normally determine massive cellular apoptosis in experimental photo-dynamic therapy. The appearance of the photo-resistance, as measured by evaluating the changes in levels of expression of pro and anti apoptotic proteins, PARP fragmentation and cell viability is 2 exclusively observed with exposure to light doses not exceeding 5–6 J /cm . Above this energy, necrosis replaces apoptosis upon photo-stimulation of U937 cells. Here, we describe the appearance of photo-resistance in hypericin-loaded U937 cells, but could not fully unravel the molecular mechanism underlying this process. However, the observed stimulation of the expression of the HSP-70 protein upon photo-induced stress may suggest its involvement in this process.