Effect of retinol on radiation- and estrogen-induced neoplastic transformation of human breast epithelial cells.
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 17beta 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 alpha 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 microl/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.
Calaf
G M
GM
Center for Radiological Research, Columbia University Medical Center, New York, NY, USA. gmc24@columbia.edu
Emenaker
N J
NJ
Hei
T K
TK
D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000528:radiation effects*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D004958:Estradiol / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D018499:Linear Energy Transfer; D051379:Mice; D008819:Mice, Nude; D009154:Mutation; D009361:Neoplasm Invasiveness / Q000473:pathology; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014801:Vitamin A / Q000494:pharmacology*; D000099169:Fos-Related Antigen 1
D004958:Estradiol; D006861:Hydrogen Peroxide; D018809:Proliferating Cell Nuclear Antigen; D016760:Proto-Oncogene Proteins c-fos; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D014801:Vitamin A; D000099169:Fos-Related Antigen 1