Chen J Y, Mak N K, Wen J M, Leung W N, Chen S C, Fung M C, Cheung N H
Department of Physics, Fudan University, Shanghai, People's Republic of China.
Photochem Photobiol. 1998 Oct;68(4):545-54.
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.
比较了替莫泊芬（中-四羟基苯基氯卟啉，mTHPC）和部花青540（MC540）对小鼠髓性白血病M1细胞和WEHI 3B（JCS）细胞的光动力效应。发现mTHPC更有效且更具选择性。在90%杀伤致死剂量（LD90）下，仅需1.3微摩尔的mTHPC和4.2千焦/平方米的光照，这比使用MC540时所需的药物浓度低20倍，光剂量小11倍。同时，与MC540相比，mTHPC对共孵育红细胞的破坏减少了三分之二，即15%。共聚焦显微镜图像显示，两种药物以非常相似的方式在细胞质内弥漫性积聚，但mTHPC在光敏化的JCS细胞中诱导了更广泛的细胞凋亡。例如，在LD90时，mTHPC几乎通过凋亡杀死所有JCS细胞，并将DNA切割成极小的150碱基对片段。相比之下，在被MC540杀死的JCS细胞中，约88%通过凋亡死亡，并且有大量的大DNA片段。相对于MC540，mTHPC在白血病细胞中引发大规模和彻底凋亡的能力可能有助于解释其效力和选择性。
