Development of human prostate cancer stem cells involves epigenomic alteration and PI3K/AKT pathway activation

Jingjing Wu1, Shundong Cang2, Christina Liu3

  • 1Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province China.

Abstract

Insights

Phenethyl isothiocynate (PEITC) induces prostate cancer stem cells by altering histone acetylation and activating the PI3K/AKT pathway. This epigenetic regulation is key to cancer stem cell development.

Area of Science:

  • Oncology
  • Epigenetics
  • Molecular Biology

Background:

  • Prostate cancer stem cells (CSCs) with self-renewal and androgen-independent growth properties were generated from LNCaP cells using phenethyl isothiocynate (PEITC).
  • The underlying signaling pathways and mechanisms driving CSC development in these spheres remain largely uncharacterized.

Purpose of the Study:

  • To investigate the role of the phosphoinositol-3 kinase (PI3K)/AKT pathway and histone acetylation in the development of prostate CSCs induced by PEITC.
  • To elucidate the molecular mechanisms by which PEITC promotes the stem cell characteristics in prostate cancer.

Main Methods:

  • Western immunoblotting was employed to quantify the expression levels of PI3K pathway components.
  • Histone acetylation levels were assessed in both the generated tumor spheres and parental LNCaP cells.

Main Results:

  • Sphere stem cells exhibited a significant 7.4-fold increase in phosphorylated AKT levels compared to LNCaP cells.
  • Elevated levels of P27 (5.4-fold increase) were observed in sphere stem cells.
  • A decrease in histone H3 lysine 9 acetylation was noted in the tumor spheres.

Conclusions:

  • PEITC treatment appears to modulate the epigenome via histone acetylation, subsequently activating the PI3K/AKT pathway in LNCaP cells.
  • This epigenetic and signaling pathway activation is implicated as a contributing mechanism in the development of prostate cancer stem cells.

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