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Arctigenin in combination with quercetin synergistically enhances the antiproliferative effect in prostate cancer cells
Author(s) -
Wang Piwen,
Phan Tien,
Gordon David,
Chung Seyung,
Henning Susanne M.,
Vadgama Jaydutt V.
Publication year - 2015
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201400558
Subject(s) - lncap , prostate cancer , androgen receptor , cancer research , pi3k/akt/mtor pathway , chemistry , protein kinase b , cell growth , cancer cell , pharmacology , cell culture , cancer , signal transduction , biology , medicine , biochemistry , genetics
Scope We investigated whether a combination of two promising chemopreventive agents arctigenin (Arc) and quercetin (Q) increases the anticarcinogenic potency at lower concentrations than necessary when used individually in prostate cancer. Methods and results Androgen‐dependent LAPC‐4 and LNCaP prostate cancer cells were treated with low doses of Arc and Q alone or in combination for 48 h. The antiproliferative activity of Arc was 10‐ to 20‐fold stronger than Q in both cell lines. Their combination synergistically enhanced the antiproliferative effect, with a stronger effect in androgen receptor (AR) wild‐type LAPC‐4 cells than in AR mutated LNCaP cells. Arc demonstrated a strong ability to inhibit AR protein expression in LAPC‐4 cells. The combination treatment significantly inhibited both AR and PI3K/Akt pathways compared to control. A protein array analysis revealed that the mixture targets multiple pathways particularly in LAPC‐4 cells including Stat3 pathway. The mixture significantly inhibited the expression of several oncogenic microRNAs including miR‐21, miR‐19b, and miR‐148a compared to control. The mixture also enhanced the inhibition of cell migration in both cell lines compared to individual compounds tested. Conclusion The combination of Arc and Q that target similar pathways, at low physiological doses, provides a novel regimen with enhanced chemoprevention in prostate cancer.