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Updated: Mar 10, 2026
An Orthotopic Murine Model of Human Prostate Cancer Metastasis
Published on: September 18, 2013
Dietary Flavonoids Luteolin and Quercetin Suppressed Cancer Stem Cell Properties and Metastatic Potential of Isolated
Pei-Hsun Tsai1, Chia-Hsiung Cheng2, Chun-Yu Lin1
1Institute of Biochemical Sciences, National Taiwan University, Taipei, Taiwan, R.O.C.
Abstract:
A highly invasive Du145-III subline was isolated by three successive passages of the parental Du145 prostate tumor cell line (Du145-P) through a Boyden chamber with matrigel-coated membrane support. Du145-III cells showed great invasion potential based on their increased ability to spread/migrate and enhanced expression/secretion of the matrix metalloproteinase 9 (MMP9). Du145-III cells exerted vasculogenic mimicry (VM) properties, reminiscent of endothelial cell characteristics and expressed elevated levels of cancer stem cell (CSC) markers, including Nanog, Sox2, CD44 and ABCG2 and ability to self-renew. Of prominence, MMP9 was required for the induction of VM and for increased stemness in Du145-III cells. Using Du145-III as a model, the effects of dietary flavonoids, luteolin and quercetin, were evaluated on stemness and invasion capacity of Du145-III cells in relation to JNK signaling pathway activation. These flavonoids depressed the malignancy of highly invasive Du145-III cells, VM, anchorage-independent spheroid formation and expression of certain CSC markers. Since luteolin and quercetin were able to target CSC cells and prevent cancer cell invasiveness, may serve as potential anti-angiogenesis and anti-metastasis agents.
Insights
Dietary flavonoids luteolin and quercetin reduce prostate cancer cell invasion and stemness. These compounds show potential as anti-metastasis and anti-angiogenesis agents by targeting cancer stem cells.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Prostate cancer cell invasiveness is a critical factor in metastasis.
- Cancer stem cells (CSCs) contribute to tumor recurrence and therapeutic resistance.
- Matrix metalloproteinase 9 (MMP9) plays a role in tumor invasion and vasculogenic mimicry (VM).
Purpose of the Study:
- To investigate the effects of dietary flavonoids luteolin and quercetin on highly invasive prostate cancer cells.
- To evaluate the impact of these flavonoids on cancer stem cell properties and invasion.
- To explore the role of MMP9 and JNK signaling in flavonoid-mediated effects.
Main Methods:
- Isolation of a highly invasive Du145-III prostate cancer cell subline.
- Assessment of cell invasion, migration, MMP9 expression, and VM.
- Analysis of CSC marker expression (Nanog, Sox2, CD44, ABCG2) and self-renewal capacity.
- Evaluation of luteolin and quercetin effects on these properties, including JNK signaling.
Main Results:
- Du145-III cells exhibited high invasiveness, MMP9 expression, VM, and CSC characteristics.
- MMP9 was essential for VM induction and enhanced stemness in Du145-III cells.
- Luteolin and quercetin significantly reduced the malignancy, VM, spheroid formation, and CSC marker expression in Du145-III cells.
- Flavonoids modulated JNK signaling pathway activation.
Conclusions:
- Luteolin and quercetin effectively suppress prostate cancer cell stemness and invasiveness.
- These flavonoids demonstrate potential as anti-angiogenesis and anti-metastasis agents.
- Targeting CSCs and inhibiting MMP9-dependent VM are key mechanisms of action.
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