Abstract

BackgroundIndole-3-carbinol, derived from Cruciferous vegetables is an estrogen receptor antagonist considered a preventive agent that is naturally present in diet. There are no previous studies on its effects in human inflammatory breast cancer or canine inflammatory mammary cancer that is the most aggressive type of breast cancer.MethodsThe aim of this study was to analyze the effect of indole-3-carbinol on a SCID mice xenograft model of canine inflammatory mammary cancer, using equivalent human oral dose as a preventive therapy in humans for 3 weeks.ResultsIndole-3-carbinol treatment decreased tumor proliferation and increased apoptosis, although tumor embolization and liver metastasis were observed in some animals. There was a characteristic subpopulation of lipid-rich cells and increased contents of select steroid hormones in tumor homogenates and serum.ConclusionsOur data reveal for the first time that the ingestion of indole-3-carbinol, as administered, diminishes proliferation and increases apoptosis of tumor cells in an experimental model of inflammatory breast cancer, although this effect could not be enough to avoid the appearance of tumor embolization and metastasis. Future clinical trials will be needed to clarify the usefulness of indole-3-carbinol in this cancer and to understand the molecular mechanisms involved.

Highlights

  • Indole-3-carbinol, derived from Cruciferous vegetables is an estrogen receptor antagonist considered a preventive agent that is naturally present in diet

  • The effect of I3C could not be enough to avoid the appearance of tumor embolization and metastasis

  • Our study suggests that both Estrone sulphate (E1SO4) and E2 can be locally synthesized, especially after I3C administration

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Summary

Introduction

Indole-3-carbinol, derived from Cruciferous vegetables is an estrogen receptor antagonist considered a preventive agent that is naturally present in diet. There are no previous studies on its effects in human inflammatory breast cancer or canine inflammatory mammary cancer that is the most aggressive type of breast cancer. Several in vitro studies with breast cancer cells showed that I3C acts by blocking estrogen receptors among other mechanisms [10, 17, 26]. There are no data on the effect of I3C in human inflammatory breast cancer (IBC) or in spontaneous and experimental canine inflammatory mammary cancer (IMC). Inflammatory breast cancer has been proposed as a natural model to study the human disease [29, 35, 36]. Spontaneous and experimental canine IMC have been associated with high levels of steroid hormones in tumor homogenates, suggesting a potential autocrine/paracrine secretion [37,38,39,40,41]

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