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Updated: Dec 18, 2025

Isolation of Cancer Stem Cells From Human Prostate Cancer Samples
Published on: March 14, 2014
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.
Background:
Human prostate cancer spheres endowed with stem cell properties have been obtained from androgen-dependent cell line LNCaP after exposure to an epigenomic modulator phenethyl isothiocynate (PEITC). Sphere cells can self-renew and grow with androgen, and also without androgen. Little is known about the signaling pathway and mechanism in the development of the stem cells in the spheres.
Methods:
Expression of phosphoinositol-3 kinase (PI3K) pathway members and histone acetylation were quantified in the tumor spheres and LNCaP cells by western immunoblotting.
Results:
The level of phosphorylated AKT was significantly increased in the sphere stem cells than the LNCaP cells at an average of 7.4 folds (range 5.8-10.7 folds), whereas the P27 level was elevated 5.4 folds (range 4.8-6.3 folds) (P < 0.05). The acetylation level on histone H3 lysine 9 was decreased.
Conclusions:
PEITC appears to regulate the epigenome through histone acetylation and activate the PI3K/AKT pathway in the LNCaP cells. This mechanism may be responsible in part for the development of the prostate cancer stem cells.
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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