Arctigenin in combination with quercetin synergistically enhances the antiproliferative effect in prostate cancer cells.
METHODS
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.


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.


CONCLUSIONS
The combination of Arc and Q that target similar pathways, at low physiological doses, provides a novel regimen with enhanced chemoprevention in prostate cancer.
Division of Cancer Research and Training, Charles R. Drew University of Medicine and Science, Los Angeles, CA, USA; Center for Human Nutrition, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Piwen
P
Wang
Tien
T
Phan
David
D
Gordon
Seyung
S
Chung
Susanne M
SM
Henning
Jaydutt V
JV
Vadgama
D000728:Androgens / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005663:Furans / Q000494:pharmacology*; D006801:Humans; D017705:Lignans / Q000494:pharmacology*; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology*; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
C410798:AR protein, human; D000728:Androgens; D000970:Antineoplastic Agents; D005663:Furans; D017705:Lignans; C550570:MIRN148 microRNA, human; C549214:MIRN19A microRNA, human; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D011944:Receptors, Androgen; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D011794:Quercetin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C071942:arctigenin
Arctigenin; Combination; MicroRNA; Prostate cancer; Quercetin