Extracts of Devil's Club (Oplopanax horridus) Exert Therapeutic Efficacy in Experimental Models of Acute Myeloid Leukemia

Abstract

Acute myeloid leukemia (AML) is a group of hematological malignancies defined by expanded clonal populations of immature progenitors (blasts) of myeloid phenotype in blood and bone marrow. Given a typical poor prognostic outlook, there is great need for novel agents with anti-AML activity. Devil’s club (Oplopanax horridus) is one of the most significant medicinal plants used among the indigenous people of Southeast Alaska and the coastal Pacific Northwest, with different linguistic groups utilizing various parts of the plant to treat many different conditions including cancer. Studies identifying medically relevant components in Devil’s club are limited. For this research study, samples were extracted in 70% ethanol before in vitro analysis, to assess effects on AML cell line viability as well as to study regulation of tyrosine phosphorylation and cysteine oxidation. The root extract displayed better in vitro anti-AML efficacy in addition to a noted anti-tyrosine kinase activity independent of an antioxidant effect. In vivo therapeutic studies using an immunocompetent murine model of AML further demonstrated that Devil’s club root extract improved the murine survival while decreasing immunosuppressive regulatory T cells and improving CD8+ T-cell functionality. This study defines for the first time an anti-AML efficacy for extracts of Devil’s club.

Anticancer Activities of Polyynes from the Root Bark of Oplopanax horridus and Their Acetylated Derivatives

“…It was found that the compounds with higher anti-proliferative activity presented more potential cytotoxic effect on normal human hepatic cells as well (Table 1), which means these compounds may have potential hepatotoxicity in vivo. Actually, the safety and efficiency of O. horridus have not been evaluated totally thus far though it has a long history of use medicinally and as a dietary supplement [21,24], so more studies are definitely needed. …”

Therapeutic effect of Northern Labrador tea extracts for acute myeloid leukemia

“…Next, the acetone extract was formulated into the drinking water of male C57BL/6J mice engrafted with C1498 cells. We have previously used this animal model of AML in experimental therapeutic studies (Barth et al, ; McGill et al, ; McGill, Brown, Cheng, et al, ). This included an evaluation of the anti‐AML efficacy of extracts from Devil's Club ( Oplopanax horridus ), which is another Alaskan medicinal plant with profound indigenous use (McGill et al, ).…”

“…Cellular viability assays were performed as previously described using a Cell Titer 96 AQueous Non‐Radioactive Cell Proliferation Assay according to the manufacturer's instructions (Promega, Madison, WI; Barth et al, ; Brown et al, ; McGill et al, ; McGill et al, ). Briefly, C1498 cells were incubated for 48 hr, whereas primary human AML samples were incubated for 96 hr, with control or experimental treatments, prior to cellular viability assays.…”

“…C57BL/6 J mice were bred from founders obtained from the Jackson Laboratory (Bar Harbor, ME). As previously described (Barth et al, ; McGill et al, ; McGill, Brown, Cheng, et al, ), male C57BL/6 J mice were engrafted with C1498 cells (1 × 10 6 cells/mouse) by retro‐orbital injection. After 12 days, mice were randomized and given ad libitum access to drinking water supplemented with the Northern Labrador tea acetone extract (1 mg/ml), or to control water, and survival was monitored.…”

Acid ceramidase is upregulated in AML and represents a novel therapeutic target

“…To generate the in vivo C1498 murine AML model, 1 x 10 6 C1498 cells were injected retro-orbitally into syngeneic eight-week-old female C57BL/6J mice (Jackson Labs, Bar Harbor, ME) [63]. LCL204 was dissolved in 30% v/v propylene glycol, 5% v/v Tween 80 and 65% of 5% w/v dextrose in water (PTD).…”