TY - JOUR
T1 - A Comparison of the Photodynamic Effects of Temoporfin (mTHPC) and MC540 on Leukemia Cells
T2 - Efficacy and Apoptosis
AU - Chen, J. Y.
AU - Mak, N. K.
AU - Wen, J. M.
AU - Leung, W. N.
AU - Chen, S. C.
AU - Fung, M. C.
AU - Cheung, N. H.
N1 - Funding information:
We thank Scotia Pharmaceuticals Ltd. for their generous gift of the inTHPC samples and the Faculty Research Grant of the Hong Kong Baptist University as well as the Croucher Foundation of Hong Kong for their support of this work.
Publisher copyright:
© 1998 American Society for Photobiology
PY - 1998/10
Y1 - 1998/10
N2 - 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 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.
AB - 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 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.
UR - http://www.scopus.com/inward/record.url?scp=0032184764&partnerID=8YFLogxK
U2 - 10.1111/j.1751-1097.1998.tb02512.x
DO - 10.1111/j.1751-1097.1998.tb02512.x
M3 - Journal article
C2 - 9796437
AN - SCOPUS:0032184764
SN - 0031-8655
VL - 68
SP - 545
EP - 554
JO - Photochemistry and Photobiology
JF - Photochemistry and Photobiology
IS - 4
ER -