INHIBITION OF TUMORAL CELL RESPIRATION AND GROWTH BY NORDIHYDROGUAIARETIC ACID

The effects of nordihydroguaiaretic acid (NDGA), best known as an inhi bitor of lipoxygenase activities, on the culture growth, oxygen consum ption, ATP level, viability, and redox state of some electron carriers of intact TA3 and 786A ascites tumor cells have been studied. NDGA in hibited the respiration rate of these two tumor cell lines by preventi ng electron flow through the respiratory chain. Consequently, ATP leve ls, cell viability and culture growth rates were decreased. NDGA did n ot noticeably inhibit electron flow through both cytochrome oxidase an d ubiquinone-cytochrome tie, complex. Also, the presence of NDGA chang ed to redox state of NAD(P)(+) to a more reduced level, and the redox states of ubiquinone, cytochrome b and cytochromes c + c(1) changed to a more oxidized level. These observations suggest that the electron t ransport in the tumor mitochondria was inhibited by NDGA at the NADH-d ehydrogenase-ubiquinone level (energy-conserving site 1). As a consequ ence, mitochondrial ATP synthesis would be interrupted. This event cou ld be related to the cytotoxic effect of NDGA.