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 merodant oin mediate their preferential cytotoxicity towards certain types of m alignant cells including human breast cancer cells in vitro and in viv o, The mechanism of cytotoxic action appears to be, in part, via initi al interaction with topoisomerase II leading to apoptosis. To further build upon these findings we now show that pMC540 and merodantoin disr upt mitochondrial morphology and function in intact MCF-7 human breast cancer cells as seen by their causing the release of rhodamine 123 fr om prestained cells, a rapid reduction in ATP levels, inhibition of su ccinate dehydrogenase activity and oxygen consumption, These data sugg est that mitochondria may also be an important target for the cytotoxi c action of pMC540 and merodantoin mediated through disruption of the energy balance.