In vitro anti-proliferative and antioxidant studies on Devil's Club Oplopanax horridus

Abstract

Devil's Club, Oplopanax horridus (OH), is a widely used folk medicine in Alaska and British Columbia for treating a variety of ailments including arthritis, fever and diabetes. HPLC profiling shows that numerous compounds are present in the 70% ethanolic extract of OH dry root bark powder. OH extract inhibited K562, HL60, MCF7 and MDA-MB-468 cell growth with the 50% inhibition (IC(50)) estimated at 1/2700, 1/1700, 1/500 and 1/2500 dilutions, respectively. Non-cytotoxic concentrations (<IC(50)) of OH extract combined with non-cytotoxic concentrations (<IC(50)) of camptothecin (CAM) or paclitaxel (PTX) were tested on the tumor cell lines. Of the 19 combinations tested, 9 showed additive or synergistic anti-proliferative effect while the rest showed antagonistic effect. Combination of OH extract at 1/4000 and 1/16,000 dilutions with 0.1 microM of CAM produced additive, anti-proliferative effects on K562 cells, as did 1/2000 and 1/1000 dilutions of OH combined with 2.5 nM of PTX on MCF7, and 1/4000 dilution of OH with 1 nM of PTX on MDA-MB-468 cells. Combination of 1/8000 and 1/4000 dilution of OH with 0.05 microM of CAM showed strong synergistic anti-proliferative effects on HL60 cells. At non-cytotoxic 1/4000 dilution, OH induced 13.1% of HL60 cells to differentiate into granulocytes but had no effect on monocyte/macrophage differentiation. A cell free hydroxyl radical scavenging assay estimated that OH at 1/100, 1/10 and 1/5 dilutions showed activities equivalent to 2.7, 15.7 and 25.6 microM of Trolox, respectively. At non-cytotoxic 1/4000 and 1/2000 dilutions, OH significantly reduced nitric oxide production by lipopolysaccharide activated RAW 264.7 cells (p<0.001). Our data show that the ethanolic extract of OH has anti-proliferative on several cancer cell lines, and has strong antioxidant activity.