The long-term goal of this proposal is to define the role of vitamin E in the prevention and treatment of cancer.
Our specific aims are: (1) to investigate whether or not the effects of vitamin E on neuroblastoma (NB) cells are mediated by cAMP (adenosine 3',5'-cyclic monophosphate)-dependent mechanisms, and (2) to investigate whether or not the enhancing effect of vitamin E on prostaglandins (PGE1 and PGA2)-induced morphological differentiation (neurite formation) of NB cells are mediated by cAMP-dependent mechanism. A murine NB clone, NBP2, will be used. D-alpha-tocopheryl (vitamin E) succinate, which has been found to be most potent form of vitamin E, will be utilized in this study. The following parameters of cAMP system will be examined after treatment of NB cells with vitamin E succinate: (1) basal adenylate cyclase (AC) activity in vitro, (2) sensitivity of AC to PGE1 and PGA2, (3) intracellular level of cAMP, and (4) cAMP-dependent phosphorylation of cellular proteins. The enhancing effect of vitamin E succinate on PGE1-and PGA2-induced morphological differentiation of NB cells will be investigated by examining alterations in PGE1- and PGA2-sensitive AC, cAMP level and cAMP-dependent phosphorylation of specific proteins. Both vitamin E and cAMP have been shown to block the action of tumor promoters and to inhibit the growth of some animal and human tumors in vivo and in vitro. Results of this study would establish whether or not the effects of vitamin E and cAMP are mediated by a common mechanism, i.e., an enhancement of cAMP-dependent phosphorylation of specific proteins. This may help in the design of cancer prevention and treatment studies.
