title: Increased chemopreventive effect by combining arctigenin, green tea polyphenol and curcumin in prostate and breast cancer cells.
abstract: The low bioavailability of most flavonoids limits their application as anti-carcinogenic agents in humans. A novel approach of treatment with a mixture of bioactive compounds that share molecular anti-carcinogenic targets may enhance the effect on these targets at low concentrations of individual compound, thereby overcoming the limitations of reduced bioavailability. We therefore investigated whether a combination of three natural products arctigenin (Arc), a novel anti-inflammatory lignan from the seeds ofArctium lappa,green tea polyphenol (-)-epigallocatechin gallate (EGCG) and curcumin (Cur) increases the chemopreventive potency of individual compounds. LNCaP prostate cancer and MCF-7 breast cancer cells were treated with 2-4 mg/L (about 5-10μM) Cur, 1μM Arc and 40μM EGCG alone or in combination for 48h. In both cell lines treatment with the mixture of Cur, Arc and EGCG synergistically increased the antiproliferative effect. In LNCaP cells both Arc and EGCG increased the pro-apoptotic effect of Cur. Whereas in MCF-7 cells Arc increased the cell apoptosis of Cur while EGCG enhanced cell cycle arrest of Cur at G0/G1phase. The strongest effects on cell cycle arrest and apoptosis were achieved by combining all three compounds in both cell lines. The combination treatment significantly increased the ratio of Bax to Bcl-2 proteins, decreased the activation of NFκB, PI3K/Akt and Stat3 pathways and cell migration compared to individual treatment. These results warrant in vivo studies to confirm the efficacy of this novel regimen by combining Arc and EGCG with Cur to enhance chemoprevention in both prostate and breast cancer.
authors.affiliation: Division of Cancer Research and Training, Charles R. Drew University of Medicine and Science, Los Angeles, CA 90059, USA ; Center for Human Nutrition, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
authors.forename: Piwen
authors.initials: P
authors.lastname: Wang
authors.affiliation: Division of Cancer Research and Training, Charles R. Drew University of Medicine and Science, Los Angeles, CA 90059, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: Division of Cancer Research and Training, Charles R. Drew University of Medicine and Science, Los Angeles, CA 90059, USA.
authors.forename: Seyung
authors.initials: S
authors.lastname: Chung
authors.affiliation: Division of Cancer Research and Training, Charles R. Drew University of Medicine and Science, Los Angeles, CA 90059, USA ; David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
authors.forename: Yanyuan
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Center for Human Nutrition, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
authors.forename: Susanne M
authors.initials: SM
authors.lastname: Henning
authors.affiliation: Division of Cancer Research and Training, Charles R. Drew University of Medicine and Science, Los Angeles, CA 90059, USA ; David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
authors.forename: Jaydutt V
authors.initials: JV
authors.lastname: Vadgama
keywords: Curcumin; arctigenin; breast cancer; combination; green tea polyphenol; prostate cancer