Genistein decreases the breast cancer stem-like cell population through Hedgehog pathway

Abstract

Insights

Genistein, a soy isoflavone, effectively inhibits breast cancer stem-like cells (BCSCs) by down-regulating the Hedgehog-Gli1 pathway. This research supports genistein

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Breast cancer stem-like cells (BCSCs) are crucial for cancer development and recurrence.
  • Genistein, a soy isoflavone, exhibits anti-tumor properties in various cancers, including breast cancer.
  • Understanding genistein's effect on BCSCs is vital for novel cancer prevention strategies.

Purpose of the Study:

  • To investigate the inhibitory effects of genistein on breast cancer stem-like cells (BCSCs).
  • To elucidate the underlying molecular mechanisms by which genistein affects BCSCs.
  • To evaluate genistein's potential in targeting BCSCs both in vitro and in vivo.

Main Methods:

  • Cell proliferation, apoptosis, and colony formation assays were performed.
  • Mammosphere formation assays and CD44/CD24 staining assessed BCSC activity in vitro.
  • A nude mouse xenograft model, real-time PCR, and immunohistochemistry evaluated in vivo effects and mechanisms.

Main Results:

  • Genistein suppressed MCF-7 breast cancer cell growth and proliferation while enhancing apoptosis.
  • Genistein significantly reduced the population of breast cancer stem cells both in vitro and in vivo.
  • The Hedgehog-Gli1 signaling pathway was identified as a key target, with genistein causing its down-regulation.

Conclusions:

  • Genistein inhibits breast cancer stem-like cells (BCSCs) by down-regulating the Hedgehog-Gli1 signaling pathway.
  • This study provides the first evidence of genistein targeting BCSCs via this pathway.
  • Findings support the clinical investigation of genistein for breast cancer treatment, specifically targeting BCSCs.

Related Concept Videos

Hedgehog Signaling Pathway02:33

Hedgehog Signaling Pathway

The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
7.1K
Hedgehog Signaling Pathway02:33

Hedgehog Signaling Pathway

1.5K
Cancer Stem Cells and Tumor Maintenance02:40

Cancer Stem Cells and Tumor Maintenance

Early diagnosis and treatment can often cure cancer. However, even with treatment, residual cells called cancer stem cells (CSC) might remain, often causing tumor recurrence. These cancer stem cells possess the potential for self-renewal and multi-lineage differentiation and are often responsible for the therapeutic resistance displayed in most cancers.
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
4.3K
Cancer Stem Cells and Tumor Maintenance02:40

Cancer Stem Cells and Tumor Maintenance

2.0K
Loss of Tumor Suppressor Gene Functions01:12

Loss of Tumor Suppressor Gene Functions

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
4.9K
Cancer-Critical Genes II: Tumor Suppressor Genes01:05

Cancer-Critical Genes II: Tumor Suppressor Genes

Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
8.3K