EFFECT OF ANTIOXIDANTS ON THE CYTOTOXICITY OF OXYGENATED STEROLS AND ANTIESTROGENS

Abstract

Oxygenated sterols and nonsteroid antiestrogens are known to have potent cytotoxic effects against many different cell types in vivo and in vitro. The cellular basis of this cytotoxic actions is not understood. In an attempt to study the cellular basis of the cytotoxic action of oxysterols and antiestrogens and to determine whether these compounds have overlapping mechanisms of action, studies were carried out to explore the possibility that these compounds kill cells via an oxidative mechanism. Using two murine lymphoma cell lines(ELA and K36) and human breast cancer cells (MCF 7), two oxysterols(7-ketocholestanol and 25- hydroxycholesterol), and two antiestrogens(tamoxifen and clomiphene), it was demonstrated that some antioxidants are capable of blocking the cytotoxic actions of both oxysterols and antiestrogens. These observations provide suggestive evidence that these two classes of compounds may share a similar mechanism of action which involves an oxidative pathway.