Dietary soy isoflavones increase metastasis to lungs in an experimental model of breast cancer with bone micro-tumors

Clin Exp Metastasis. 2015 Apr;32(4):323-33. doi: 10.1007/s10585-015-9709-2. Epub 2015 Mar 8.


Bone is one of the most common sites for metastasis in breast cancer (BC). Micro-metastasis in bone marrow was detected in 30% of patients with stage I, II, or III BC at primary surgery and is a strong indicator of poor prognosis. The role dietary soy isoflavones play in BC with bone micro-metastasis is unclear. In this study, we examined the effects of genistein, daidzein, (-)-equol or a mixture of soy isoflavones on BC with bone micro-metastasis using an experimental model of murine mammary cancer 4T1 cells engineered with luciferase. A small number (1000) of 4T1 cells were injected into the tibia of female Balb/c mice to establish micro-tumors in bone. Soy isoflavones were supplemented in the AIN-93G diet at 750 mg/kg and were provided to mice from 3 weeks before to 3 weeks after cell injection. Bioluminescent imaging was conducted on day 2 (D2), D6, D8, D16 and D20 post cell injection and the results indicated dietary soy isoflavones enhanced the growth of bone micro-tumors on D8. Furthermore, dietary soy isoflavones stimulated metastatic tumor formation in lungs and increased Ki-67 protein expression in these metastasized tumors. In vitro, soy isoflavones (<10 µM) had limited effects on the growth, motility or invasion of 4T1 cells. Thus, the in vivo stimulatory effect could be likely due to systemic effects between the host, 4T1 tumors and soy isoflavones. In conclusion, soy isoflavones stimulate BC with bone micro-metastasis in mice and further investigations are needed regarding their consumption by BC survivors.

Publication types

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

MeSH terms

  • Animals
  • Anticarcinogenic Agents / pharmacology
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / mortality
  • Bone Neoplasms / secondary
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Cell Proliferation / drug effects
  • Diet
  • Dietary Supplements
  • Disease Models, Animal
  • Equol / blood
  • Equol / pharmacology
  • Female
  • Genistein / blood
  • Genistein / pharmacology
  • Isoflavones / administration & dosage
  • Isoflavones / blood*
  • Isoflavones / pharmacology*
  • Ki-67 Antigen / metabolism
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / secondary
  • Mice
  • Mice, Inbred BALB C
  • Neoplasm Invasiveness / pathology
  • Neoplasm Transplantation
  • Prognosis
  • Random Allocation
  • Soy Foods


  • Anticarcinogenic Agents
  • Isoflavones
  • Ki-67 Antigen
  • Mki67 protein, mouse
  • Equol
  • daidzein
  • Genistein