Background: Breast cancer is an increasingly common malignancy. Several vitamins such as retinoic acid (RA), ascorbic acid (AA), vitamin D and vitamin E are known to prevent the development and progression of breast cancer. Objective: We sought to determine whether RA and AA together (RA+AA) acted synergistically in blocking the proliferation of human breast cancer cells. To elucidate the mechanism by which RA+AA inhibited breast carcinoma proliferation, we then evaluated the gene expression profiles of the treated and untreated cells by radioactive cDNA microarray analysis. Methods: We cultured the human breast cancer cell line MCF-7 for 3 days with 100 nM RA and/or 1 mM AA, counted the cell numbers and harvested the total RNAs for cDNA microarray analysis. Results: RA, AA and RA+AA reduced MCF-7 cell proliferation by 20.7%, 23.3% and 75.7% relative to the untreated cell proliferation, respectively. The synergistic ratio of RA and AA was 1.72. The MCF-7 gene expression profiles showed that 29 genes were up-regulated and 38 genes were down-regulated after RA+AA treatment. The nature of these genes suggests that the mechanism by which RA and AA act synergistically in inhibiting human breast cancer cell proliferation may involve the expression of genes that induce differentiation and block proliferation, and the up-regulation of antioxidant enzymes and proteins involved in apoptosis, cell cycle regulation and DNA repair. Conclusion: Combined treatment with RA and AA inhibits the proliferation of human breast cancer cells by altering their gene expression related to antioxidation processes as well as the proliferation inhibitory pathway.
Bibliographical noteFunding Information:
This study was financially supported by the Korea Science and Engineering Foundation (grant no. R01-2001-000-00212-0); was supported by a grant from the Medical Research Center for Environmental Toxicogenomic and Proteomics, funded by the Korea Science and Engineering Foundations and Ministry of Science and Technology; a grant from the Korea Health 21 R&D Project, Ministry of Health and Welfare, Republic of Korea (Hmp-00-GN-01-0002 & KPGRN-R-04); the Korea Institute of Science and Technology Evaluation and Planning and Ministry of Science and Technology, Korean government, through its National Nuclear Technology Program. We thank Dr. Yoon S. Cho-Chung (Cellular Biochemistry Section, Basic Research Laboratory, CCR, NCI, NIH, Bethesda, MD) and Kevin G. Becker (DNA Array Unit, NIA, NIH, Baltimore, MD) for valuable advice about the cDNA microarray analysis. In addition, we are grateful to Seung-Ho Lee, Yeon-Mi Rhyu, Sung-Hwa Sohn, Sang-Hee Seo and Yu-Ri Kim (Department of Biochemistry and Molecular Biology, Korea University Medical College, Seoul, Korea) for their technical assistance in this investigation.
- Ascorbic acid
- Combined treatment of vitamins
- Human breast cancer
- Retinoic acid
- cDNA microarray
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Molecular Biology
- Nutrition and Dietetics
- Clinical Biochemistry