Background: Retinoids are effective in reducing transformation of various cell types; however the role of lipid peroxidation has not been studied in this regard.
Materials and methods: Retinoic acid (RA) and retinol were tested on several SV-40 large-T-antigen transformed bovine mammary fibroblast (MFB) lines that form foci on plastic with long-term culture.
Results: Dose response studies revealed that RA at 10(-6) M was the most potent dose in delaying the onset of foci formation and reducing total foci number. RA was always more effective than retinol. Addition of RA (10(-6) M) to MFB cells increased lipid peroxide (LPO) concentrations by approximately three-fold relative to untreated MFB cells or to RA or control treated normal mammary fibroblasts. The lipoxygenase inhibitor, nordihydroguaiaretic acid (NDGA), acted synergistically with RA to increase LPO and cell death in MFB cells. The combination of the cyclooxygenase inhibitor, indomethacin, at 10(-4) M with 10(-6) M RA lowered MFB fibroblast cell numbers when compared to fibroblasts cultured singly with either RA or indomethacin.
Conclusions: These data indicate that an increase in lipid peroxidation occurs specifically in tumor cells treated with RA and this may play a role in RA-mediated suppression of cellular transformation in the mammary gland. Additionally, eicosanoid inhibitors may have an additive or synergistic effect with RA on the inhibition of mammary tumor cell transformation and proliferation.