By analyzing the gene expression profile between tumor cells and revertant counterparts that have a suppressed malignant pheno-type, we previously reported a significant down-regulation of translationally controlled tumor protein (TCTP) in the revertants. In the present study, we derived, by using the H1 parvovirus as a selective agent revertants from three major solid cancers: colon, lung, and melanoma cell lines. These cells have a strongly sup- pressed malignant phenotype both in vitro and in vivo. The level of TCTP is decreased in most of the revertants. To verify whether inhibition of TCTP expression induces changes in the malignant phenotype, in the classical, well established model of "flat reversion," v-src-transformed NIH3T3 cells were transfected with anti-sense TCTP. By inhibiting the expression of TCTP, the number of revertant cells was raised to 30%, instead of the reported rate for spontaneous flat revertants of 10-6. Because Tap encodes for a histamine-releasing factor, we tested the hypothesis that inhibitors of the histaminic pathway could be effective against tumor cells. We show that some antihistaminic compounds (hydroxyzine and promethazine) and other pharmacological compounds with a related structure (including thioridazine and sertraline) kill tumor cells and significantly decrease the level of TCTP. All together, these data suggest that with tumor reversion used as a working model, TaP was identified as a target and drugs were selected that decrease its expression and kill tumor cells. [ABSTRACT FROM AUTHOR]