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 potent and selective. At a lethal dosage of 90% killing (LD90), only 1.3 microM of mTHPC and 4.2 kJ/m2 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 MC540. Confocal micrographs showed that both drugs accumulated diffusely 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 cleaved the DNA to extremely small 150 base-pair fragments. In contrast, among the JCS cells killed by MC540, about 88% died via apoptosis and large DNA fragments were abundant. Relative to MC540, the ability of mTHPC to trigger large-scale and thorough apoptosis in leukemia cells may help explain its potency and selectivity.
Chen
J Y
JY
Department of Physics, Fudan University, Shanghai, People's Republic of China. nhcheung@hkbu.edu.hk
Mak
N K
NK
Wen
J M
JM
Leung
W N
WN
Chen
S C
SC
Fung
M C
MC
Cheung
N H
NH
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects* / Q000528:radiation effects; D004912:Erythrocytes / Q000187:drug effects* / Q000528:radiation effects; D007942:Leukemia, Experimental; D007951:Leukemia, Myeloid; D008027:Light; D008652:Mesoporphyrins / Q000633:toxicity*; D051379:Mice; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000633:toxicity*; D011744:Pyrimidinones / Q000633:toxicity; D014407:Tumor Cells, Cultured
D008652:Mesoporphyrins; D017319:Photosensitizing Agents; D011744:Pyrimidinones; C003954:merocyanine dye; C072269:temoporfin