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

We have observed that exposure of U937 cells, pre-incubated for 18 h with 0.2 μM hypericin, to 599 nm laser radiation with a fluence of 2.5 J/cm2 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 exclusively observed with exposure to light doses not exceeding 5–6 J/cm2. 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.