A Comparison of the Photodynamic Effects of Temoporfin (mTHPC) and MC540 on Leukemia Cells: Efficacy and Apoptosis |
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Authors: | J. Y. Chen N. K. Mak J. M. Wen W. N. Leung S. C. Chen M. C. Fung N. H. Cheung |
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Affiliation: | Department of Physics, Fudan University, Shanghai, People's Republic of China;department of Biology, Hong Kong Baptist University, Waterloo Road, Hong Kong;department of Pathology, School of Basic Medicine, Sun Yat-Sen University of Medical Sciences, People's Republic of China;department of Physics, Hong Kong Baptist University, Waterloo Road, Hong Kong;department of Biology, The Chinese University of Hong Kong, Shatin, Hong Kong |
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Abstract: | The photodynamic effects of temoporfin (meso-tetrahy-droxyphenylchlorin, 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 μM 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. |
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