Glucarate is a potential non-toxic anti-tumor agent which also interacts at sub-optimal (i.e. ineffective) doses, synergistically with other agents such as N-(4-hydroxyphenyl)retinamide (HPR) to inhibit tumor growth and in fact cause tumor shrinkage. When given p.o. glucarate is given in a sustained release form. The present investigation focuses on the chemotherapeutic effects of glucarate in combination with HPR on the 7,12-dimethylbenz(a) anthracene-induced rat mammary tumor in vivo and the human breast cancer MCF-7 cell line in vitro. The purpose of this investigation is to optimize the synergistic interaction of glucarate and HPR in the mammary cancer system in such a way as to determine whether glucarate acts as an adjuvant in its synergism with other agents or as an effector. Two theories are evaluated: (i) Glucarate alters the metabolism of HPR or other agents so as to increase their anti-tumor cell activity and (ii) Glucarate directly or indirectly alters the tumor cells themselves so as to enhance the anti-tumor action of HPR. The study takes advantage of hormone sensitive and insensitive mammary tumor cell systems in vivo and in vitro.
