Isoflavones in soy flour diet have different effects on whole-genome expression patterns than purified isoflavone mix in human MCF-7 breast tumors in ovariectomized athymic nude mice

Mol Nutr Food Res. 2015 Aug;59(8):1419-30. doi: 10.1002/mnfr.201500028. Epub 2015 Jun 26.

Abstract

Scope: Soy flour diet (MS) prevented isoflavones from stimulating MCF-7 tumor growth in athymic nude mice, indicating that other bioactive compounds in soy can negate the estrogenic properties of isoflavones. The underlying signal transduction pathways to explain the protective effects of soy flour consumption were studied here.

Methods and results: Ovariectomized athymic nude mice inoculated with MCF-7 human breast cancer cells were fed either Soy flour diet (MS) or purified isoflavone mix diet (MI), both with equivalent amounts of genistein. Positive controls received estradiol pellets and negative controls received sham pellets. GeneChip Human Genome U133 Plus 2.0 Array platform was used to evaluate gene expressions, and results were analyzed using bioinformatics approaches. Tumors in MS-fed mice exhibited higher expression of tumor growth suppressing genes ATP2A3 and BLNK and lower expression of oncogene MYC. Tumors in MI-fed mice expressed a higher level of oncogene MYB and a lower level of MHC-I and MHC-II, allowing tumor cells to escape immunosurveillance. MS-induced gene expression alterations were predictive of prolonged survival among estrogen-receptor-positive breast cancer patients, whilst MI-induced gene changes were predictive of shortened survival.

Conclusion: Our findings suggest that dietary soy flour affects gene expression differently than purified isoflavones, which may explain why soy foods prevent isoflavones-induced stimulation of MCF-7 tumor growth in athymic nude mice.

Keywords: Breast cancer; Isoflavones; MCF-7; Soy; Whole-genome expression.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Antineoplastic Agents, Phytogenic / administration & dosage*
  • Antineoplastic Agents, Phytogenic / adverse effects
  • Antineoplastic Agents, Phytogenic / analysis
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Breast Neoplasms / diet therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cluster Analysis
  • Computational Biology
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Genistein / administration & dosage
  • Genistein / adverse effects
  • Genistein / analysis
  • Genistein / therapeutic use
  • Humans
  • Isoflavones / administration & dosage*
  • Isoflavones / adverse effects
  • Isoflavones / analysis
  • Isoflavones / therapeutic use
  • MCF-7 Cells
  • Neoplasm Proteins / agonists
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Oligonucleotide Array Sequence Analysis
  • Ovariectomy
  • Phytoestrogens / administration & dosage*
  • Phytoestrogens / adverse effects
  • Phytoestrogens / analysis
  • Phytoestrogens / therapeutic use
  • Random Allocation
  • Soy Foods / analysis*
  • Tumor Burden
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents, Phytogenic
  • Isoflavones
  • Neoplasm Proteins
  • Phytoestrogens
  • daidzein
  • Genistein