EFFECTS OF NON-PHORBOL TUMOR PROMOTERS AND RELATED POLYPHENOLIC COMPOUNDS ON CELL-CELL COMMUNICATION (IODOACETIC ACID, ANTHRALIN, HYDROQUINONE)

ERWIN CHUN-CHIT SI, Purdue University

Abstract

Recently, in vitro metabolic cooperation between lung fibroblasts, which reflects cell-cell communication, has been suggested as a screening test for tumor promoters. The present study was initiated to examine the effects of a number of non-phorbol tumors promoters, including anthralin (ANTH) and iodoacetic acid (IODO), on cell-cell communication using a citrulline incorporation assay. Some structurally and functionally related compounds such as hydroquinone (HQ) and 2-hydroxyestrone (2-HE) were also examined. 12-O-Tetradecanoylphorbol-13-acetate (TPA), a potent skin tumor promoter, inhibited the cell-cell communication at 7 ng/ml (11 nM). However, of the four other compounds tested, namely, ANTH, IODO, HQ, and 2-HE, none had an effect on the process even at cytotoxic concentrations. Another form of cell-cell communication occurs during the course of phytohemagglutinin (PHA)-induced lymphocyte blastogenesis. It was monitored by the degree of cellular agglutination measured spectrophotometrically at 620 nm. ANTH, HQ, and 2-HE inhibited the PHA-induced lymphocyte agglutination at micromolar concentrations while IODO was devoid of any effects at concentrations up to 100 uM. All four compounds caused a concentration-dependent suppression of PHA-induced lymphocyte blastogenesis with varying potency. ANTH significantly suppressed the process at 0.1 uM while the suppression by HQ and 2-HE were significant at micromolar concentrations. IODO, being a weak tumor promoter, was also the weakest suppressor of the process. It significantly suppressed the process at 10 uM. 1,8-Dihydroxyanthraquinone, and ANTH analogue that is inactive as a tumor promoter, failed to inhibit both blastogenesis and agglutination. The concomitant suppression of PHA-induced agglutination and blastogenesis by HQ, but not that by ANTH was prevented by the addition of 100 uM of dithiothreitol, a sulfhydryle (SH) compound. This finding suggests the suppression of these two processes by anthralin is not through the interaction of SH groups in the membrane. This notion is further substantiated by the inability of anthralin to inhibit microtubule assembly, a SH-independent process. In summary, these studies suggest that, unlike TPA, the weaker, non-phorbol tumor promoters do not inhibit cell-cell communication in the metabolic cooperation assay. Although the mechanisms of actions are diverse, they all inhibit the in vitro immune functions.

Degree

Ph.D.

Subject Area

Pharmacology

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