STUDIES ON THE EFFECTS OF POLYUNSATURATED FATTY ACIDS AND SOME NATURAL PRODUCTS ON INTERLEUKIN-2 LEVELS AND CELL PROLIFERATION IN NORMAL AND ABNORMAL HUMAN LYMPHOCYTES

Abstract

Flavonoids are natural polyphenolic compounds found ubiquitously in the plant kingdom. They are present in fruits, leafy vegetables, roots, spices, herbs and in wine. Hence flavonoids are easily accessible to humans through their diet. These polyphenolic compounds have long been shown to exert many biological and pharmacological effects and they are generally non-toxic. They would therefore be suitable compounds for possible development as therapeutic agents. The present study demonstrated some in vitro biological properties of flavonoids. Freshly isolated normal human lymphocytes, together with malignant (Molt-4) and non-malignant (IM-9) cultured cell lines were used in this study. The polyphenols exerted varying degrees of antiproliferative effects on different cell lines. Amongst the eleven test compounds studied, Lannie acid showed potent inhibitory action on normal lymphocytes cell growth and the level of IL-2 was also inhibited. The inhibitory action of these compounds was close dependent. Four potent test compounds were selected and tested on human leukemic cultured cell lines. Although these compounds were effective in inhibiting Molt-4 cell growth, they do not affect the IM-9 cells. Interestingly, these compounds also stimulated the production of IL-2 in Molt-4 cells. The effects of Lannie acid and lL-2 on DNA, RNA and protein synthesis in MolL-4 cells were studied. Both compounds were able to inhibit the incorporation of [14C] thymidine and [14C] uridine into Molt-4 cell DNA, RNA respectively and this effect was hyphenated. However, the protein synthesis was not drastically affected. Hence, it was postulated that the antiproliferative effects of these compounds could be exerted initially through the inhibition of DNA and RNA synthesis. The cytotoxic action of IL-2 and tannic acid were shown to be related to their prooxidant potential. However, lL-2 behaved as a potent prooxidant and showed greater stimulation of lipid peroxidation and free radical generation. Since tannic acid could also affect the cellular enzyme, protein kinase C, the antiproliferative action of tannic acid may be related in part to its effect on the regulation of PKC activity. The inhibitory effect of PUPAs on normal and abnormal (Molt-4) lymphocytes were also investigated. GLA, a potent inhibitor behaved like tannic acid on normal and abnormal human lymphocytes. GLA and IL-2 were able to enhance · lipid peroxidation and free radical generation on both types of cells. Hence, the cytotoxicity exhibited by GLA was mainly due to its prooxidant property.