Relationship of mitochondrial function and cellular adenosine triphosphate levels to pMC540 and merodantoin cytotoxicity in MCF-7 human breast cancer cells.
In previous studies we have reported that preactivated merocyanine 540 (pMC540) and its chemically synthesized isolates merocil and merodantoin mediate their preferential cytotoxicity towards certain types of malignant cells including human breast cancer cells in vitro and in vivo. The mechanism of cytotoxic action appears to be, in part, via initial interaction with topoisomerase II leading to apoptosis. To further build upon these findings we now show that pMC540 and merodantoin disrupt mitochondrial morphology and function in intact MCF-7 human breast cancer cells as seen by their causing the release of rhodamine 123 from prestained cells, a rapid reduction in ATP levels, inhibition of succinate dehydrogenase activity and oxygen consumption. These data suggest that mitochondria may also be an important target for the cytotoxic action of pMC540 and merodantoin mediated through disruption of the energy balance.
Gulliya
K S
KS
Baylor Research Institute, Baylor University Medical Center, Dallas, TX 75226, USA.
Sharma
R
R
Liu
H W
HW
Arnold
L
L
Matthews
J L
JL
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D005031:Ethylenethiourea / Q000031:analogs & derivatives* / Q000494:pharmacology; D005456:Fluorescent Dyes; D006801:Humans; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D010101:Oxygen Consumption / Q000187:drug effects; D011744:Pyrimidinones / Q000494:pharmacology*; D020112:Rhodamine 123; D012235:Rhodamines; D013385:Succinate Dehydrogenase / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D005456:Fluorescent Dyes; D011744:Pyrimidinones; D012235:Rhodamines; C089291:merodantoin; D020112:Rhodamine 123; D005031:Ethylenethiourea; C003954:merocyanine dye; D000255:Adenosine Triphosphate; D013385:Succinate Dehydrogenase