Effect of retinol on radiation- and estrogen-induced neoplastic transformation of human breast epithelial cells

Abstract

Clinical, epidemiological and experimental findings have provided evidence supporting a role of free radicals in the etiology of cancer. Free radical production is enhanced in many disease states, by carcinogen exposure, and under conditions of stress contributing widely to cancer development in humans. We have established an experimental breast cancer model to examine the effects of all-trans-retinol (retinol/ vitamin A) on the production of free radicals in human breast epithelial cells induced by high linear energy transfer (LET)radiation in the presence of 17ß estradiol. The following cell lines were used in these studies: the MCF-10F cell line, a spontaneously immortalized human breast epithelial cell line. Alpha 5 derived from MCF-10F cells irradiated with two separated doses of 60 cGy • particles in the presence of estrogens (60E/60E). Tumor 2, from a tumor formed in nude mice after injection with the cell line Alpha 5. Tumor 3, from secondary tumor formed from injecting Tumor 2 cells into nude mice. Each of the cell types examined had significantly elevated H 2 O 2 production levels compared to MCF-10F control cells (p<0.001). Retinol (1 µl/ml) significantly (p<0.05) decreased H 2 O 2 production in all cell types examined. Retinol significantly decreased (p<0.05) invasive capabilities of cells across matrigel coated invasion chambers and significantly reduced (p<0.05) PCNA, Fra-1, mutant p53 and increased Rb protein expression levels in comparison to non-retinol-treated ones when assayed using immunofluorescent staining coupled with confocal microscopy. The reduced H 2 O 2 production, decrease in cell invasive capabilities and alterations in protein expression levels suggest that retinol can be used as a chemopreventive agent in human breast cancer.

Prognostic Significance of New Immunohistochemistry Scoring of p53 Protein Expression in Cutaneous Squamous Cell Carcinoma of Mice

“…Vitamin A (all‐trans‐retinol) reduces free radical production and decreases the expression of the p53 protein. This has also been seen in an experimental study in breast cancer 18 …”

Plasma and Dietary Carotenoids Are Associated with Reduced Oxidative Stress in Women Previously Treated for Breast Cancer

“…Carotenoids have been shown to inhibit proliferation of transformed cells (45,46), to reduce inflammatory response (31), and, indirectly through conversion to retinol, to induce epithelial cell differentiation (47,48). In addition, although greater intake of fruits and vegetables is consistently associated with higher plasma carotenoid concentrations (49)(50)(51) and has been shown in the parent WHEL cohort (24), it may be the combination of carotenoids and other bioactive food components and nutrients found in these plant foods that affords protection.…”

Metastatic suppressor CD44 is related with oxidative stress in breast cancer cell lines

“…A pre-existent in vitro human breast epithelial cell cancer progression model from our laboratory (15,16), was used in this study to examine the metastatic potential of two tumorigenic cell lines with different phenotypes of malignancy. Previous studies of this model (17) reported a cell cycle arrest in a cell line called Alpha5 associated with high concentration of basal ROS, measured by hydrogen peroxide levels, and overexpression of basal manganese superoxide dismutase (MnSOD) enzyme.…”