A COMPARISON OF THE PHOTODYNAMIC EFFECTS OF TEMOPORFIN (MTHPC) AND MC540 ON LEUKEMIA-CELLS - EFFICACY AND APOPTOSIS

The photodynamic effects of temoporfin (meso-tetrahydroxyphenylchlorin , mTHPC) and merocyanine 540 (MC540) in murine myeloid leukemia M1 and WEHI 3B (JCS) cells were compared. The mTHPC was found to be more pot ent and selective. At a lethal dosage of 90% killing (LD90), only 1.3 mu M of mTHPC and 4.2 kJ/m(2) of light irradiation was required, which was a 20-fold lower drug concentration and 11-fold smaller light dose than that required when using MC540. Meanwhile, three times less, or 15%, of the coincubated erythrocytes were destroyed by mTHPC than by M C540. Confocal micrographs showed that both drugs accumulated diffusel y inside the cytoplasm in a very similar fashion, but mTHPC induced a more extensive apoptosis in photosensitized JCS cells. For example, at LD90, mTHPC practically killed all JCS cells via apoptosis and cleave d the DNA to extremely small 150 base-pair fragments. In contrast, amo ng the JCS cells killed by MC540, about 88% died via apoptosis and lar ge DNA fragments were abundant, Relative to MC540, the ability of mTHP C to trigger large-scale and thorough apoptosis in leukemia cells may help explain its potency and selectivity.