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Anticancer Res. 2016 Dec;36(12):6367-6380.

Dietary Flavonoids Luteolin and Quercetin Suppressed Cancer Stem Cell Properties and Metastatic Potential of Isolated Prostate Cancer Cells.

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Institute of Biochemical Sciences, National Taiwan University, Taipei, Taiwan, R.O.C.
Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan, R.O.C.
Department of Marine Biotechnology, National Kaohsiung Marine University, Kaohsiung, Taiwan, R.O.C.
Department of Nursing, Ching-Kuo Institute of Management and Health, Keelung, Taiwan, R.O.C.
Castle Hills Health Center, Saskatoon, SK, Canada.
Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan, R.O.C.
Institute of Physiology, National Yang-Ming University, Taipei, Taiwan, R.O.C.
Institute of Molecular and Cellular Biology, National Taiwan University, Taipei, Taiwan, R.O.C.
Institute of Biochemical Sciences, National Taiwan University, Taipei, Taiwan, R.O.C.


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.


Luteolin; cancer stem cell; metastasis; prostate cancer; quercetin; vasculogenic mimicry

[Indexed for MEDLINE]

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