title: 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.
authors.affiliation: Department of Pathology and Pediatrics, Center for Complementary Medicine Research, BC Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada. jtai@interchange.ubc.ca
authors.forename: Joseph
authors.initials: J
authors.lastname: Tai
authors.forename: Susan
authors.initials: S
authors.lastname: Cheung
authors.forename: Stefanie
authors.initials: S
authors.lastname: Cheah
authors.forename: Edwin
authors.initials: E
authors.lastname: Chan
authors.forename: David
authors.initials: D
authors.lastname: Hasman
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D018922:HL-60 Cells; D006801:Humans; D007198:Indians, North American; D020014:K562 Cells; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008519:Medicine, Traditional; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D028002:Oplopanax / Q000737:chemistry*; D018384:Oxidative Stress / Q000187:drug effects; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry
chemical_list: D000975:Antioxidants; D008070:Lipopolysaccharides; D010936:Plant Extracts; D009569:Nitric Oxide