GROWTH SUPPRESSION AND TOXICITY INDUCED BY CAFFEIC ACID PHENETHYL ESTER (CAPE) IN TYPE-5 ADENOVIRUS-TRANSFORMED RAT EMBRYO CELLS CORRELATE DIRECTLY WITH TRANSFORMATION PROGRESSION

The active component of the honeybee hive product propolis, caffeic ac id phenethyl ester (CAPE), induces a selective growth suppressive and toxic effect toward cloned rat embryo fibroblast cells transformed by adenovirus type 5 (Ad5) or the Ad5 E1A transforming gene versus untran sformed cloned rat embryo fibroblast cells (Z-z. Su et al., Mol. Carci nog., 4: 231-242, 1991). The present study was conducted to determine whether CAPE-induced growth suppression/toxicity was a direct result o f expression of the Ad5 E1A and E1B transforming genes or a consequenc e of the action of these genes resulting in the transformed state. For this investigation we used somatic cell hybrids and 5-azacytidine-tre ated Ad5-transformed rat embryo cells that display different stages of expression of the transformed phenotype. This series of cell lines ha s permitted us to determine whether expression of the transformed stat e and the stage of transformation progression regulates CAPE sensitivi ty. Evidence is presented indicating that sensitivity to CAPE is direc tly determined by the state of expression of the transformed progressi on phenotype, as opposed to simply the expression of the Ad5 E1A and E 1B transforming genes. These results provide further evidence that CAP E may represent a unique compound that can specifically target progres sed transformed cells for growth suppression and toxicity. An understa nding of the mechanism underlying this selective effect of CAPE could result in the identification of important biochemical pathways mediati ng cellular transformation and progression of the transformed state.