Retinoic acid and ascorbic acid act synergistically in inhibiting human breast cancer cell proliferation

Ki Nam Kim, Jae Eun Pie, Jin Hee Park, Yoon Hee Park, Hye Won Kim, Meyoung kon Kim

    Research output: Contribution to journalArticlepeer-review

    33 Citations (Scopus)


    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.

    Original languageEnglish
    Pages (from-to)454-462
    Number of pages9
    JournalJournal of Nutritional Biochemistry
    Issue number7
    Publication statusPublished - 2006 Aug


    • Anti-proliferation
    • Ascorbic acid
    • Combined treatment of vitamins
    • Human breast cancer
    • Retinoic acid
    • cDNA microarray

    ASJC Scopus subject areas

    • Endocrinology, Diabetes and Metabolism
    • Biochemistry
    • Molecular Biology
    • Nutrition and Dietetics
    • Clinical Biochemistry


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