Differential action of polyunsaturated fatty acids and eicosanoids on bleomycin-induced cytotoxicity to neuroblastoma cells and lymphocytes

INTRODUCTION: This study was conducted to examine whether bleomycin-induced growth inhibitory action on human neuroblastoma cells (IMR-32) is influenced by anti-inflammatory metabolites of polyunsaturated fatty acids (PUFAs): lipoxin A4 (LXA4), resolvin D1 and protectin D1 in vitro. MATERIAL AND METHODS: The in vitro study was conducted using monolayer cultures of exponentially growing IMR-32 cells. The effects of various PUFAs and eicosanoids and anti-inflammatory metabolites of PUFAs such as lipoxin A4 (LXA4), resolvin D1 and protectin D1 on the growth of IMR-32 cells and human lymphocytes in vitro were investigated. The potential of PUFAs, eicosanoids and LXA4, resolvin D1 and protectin D1 to modify the growth inhibitory effects of bleomycin was also studied in IMR-32 cells and human lymphocytes. RESULTS: PUFAs inhibited the growth of IMR-32 cells (EPA > DHA = AA > GLA = ALA > DGLA = LA) significantly (p < 0.001) while prostaglandins were found to be not effective. Bleomycin-induced growth inhibitory action on IMR-32 cells was augmented by PUFAs and its metabolites (p < 0.05). PUFAs and LXA4 did not inhibit the growth of human lymphocytes and bleomycin-induced growth inhibitory action was also not enhanced by these bioactive lipids. CONCLUSIONS: Bioactive lipids have differential action on normal human lymphocytes and tumor cells in vitro. The apparent lack of effect of PUFAs in combination with bleomycin on the growth of human lymphocytes in comparison to their growth inhibitory action on IMR-32 cells suggests that PUFAs can be used in combination with bleomycin to target tumor cells with little concern over this combination’s effect on the growth of human lymphocytes. Further studies are warranted to evaluate these differential effects under in vivo conditions.