Growth inhibition of human acute lymphoblastic CCRF-CEM leukemia cells by medicinal plants of the West-Canadian Gwich’in Native Americans

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Abstract

The Gwich’in, which belong to the Athapaskan language group of Native Americans live in the borderland between Alaska and Canada. We analyzed 29 medicinal plants of this tribe for their growth inhibitory activity against CCRF-CEM T-cell acute lymphoblastic leukemia (T-ALL) cells. The anti-leukemic activity of these plants has not been investigated as yet. Considering the poor cure rates of some ALL forms, there might be a great potential for medicinal plants as resource for natural products to treat T-ALL. We found that the hexane extracts of three plants revealed considerable growth inhibition on CCRF-CEM cells. The 50% inhibition concentrations (IC ₅₀) were 6.63 ± 0.03 µg/ml for Cladina mitis, 8.65 ± 0.38 µg/ml for Picea mariana (needles), and 9.67 ± 1.36 µg/ml for Artemisia frigida. Further investigations are required to isolate the active constituents of these plants.

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Most cited references 23

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From traditional Chinese medicine to rational cancer therapy.

Thomas Efferth, Paul C.H. Li, Venkata Konkimalla … (2007)

Many natural products and derivatives thereof belong to the standard repertoire of cancer chemotherapy. Examples are Vinca alkaloids, taxanes and camptothecins. In recent years, the potential of natural products from plants, notably from medicinal plants used in traditional Chinese medicine (TCM), has been recognized by the scientific community in the Western world. To provide an example of the most recent developments in this field, we have selected several compounds, namely artesunate, homoharringtonine, arsenic trioxide and cantharidin, that are found in natural TCM products and that have the potential for use in cancer therapy. Controlled clinical studies have shown that homoharringtonine and arsenic trioxide can exert profound activity against leukaemia. Increased knowledge of the molecular mechanisms of TCM-derived drugs and recent developments in their applications demonstrate that the combination of TCM with modern cutting-edge technologies provides an attractive strategy for the development of novel and improved cancer therapeutics.

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Screening of chemical composition, antimicrobial and antioxidant activities of Artemisia essential oils.

Daise Lopes-Lutz, Daniela Alviano, Celuta Alviano … (2008)

The chemical composition of essential oils isolated from aerial parts of seven wild sages from Western Canada -Artemisia absinthium L., Artemisia biennis Willd., Artemisia cana Pursh, Artemisia dracunculus L., Artemisia frigida Willd., Artemisia longifolia Nutt. and Artemisia ludoviciana Nutt., was investigated by GC-MS. A total of 110 components were identified accounting for 71.0-98.8% of the oil composition. High contents of 1,8-cineole (21.5-27.6%) and camphor (15.9-37.3%) were found in Artemisia cana, A. frigida, A. longifolia and A. ludoviciana oils. The oil of A. ludoviciana was also characterized by a high content of oxygenated sesquiterpenes with a 5-ethenyltetrahydro-5-methyl-2-furanyl moiety, of which davanone (11.5%) was the main component identified. A. absinthium oil was characterized by high amounts of myrcene (10.8%), trans-thujone (10.1%) and trans-sabinyl acetate (26.4%). A. biennis yielded an oil rich in (Z)-beta-ocimene (34.7%), (E)-beta-farnesene (40.0%) and the acetylenes (11.0%) (Z)- and (E)-en-yn-dicycloethers. A. dracunculus oil contained predominantly phenylpropanoids such as methyl chavicol (16.2%) and methyl eugenol (35.8%). Artemisia oils had inhibitory effects on the growth of bacteria (Escherichia coli, Staphylococcus aureus, and Staphylococcus epidermidis), yeasts (Candida albicans, Cryptococcus neoformans), dermatophytes (Trichophyton rubrum, Microsporum canis, and Microsporum gypseum), Fonsecaea pedrosoi and Aspergillus niger. A. biennis oil was the most active against dermatophytes, Cryptococcus neoformans, Fonsecaea pedrosoi and Aspergillus niger, and A. absinthium oil the most active against Staphylococcus strains. In addition, antioxidant (beta-carotene/linoleate model) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activities were determined, and weak activities were found for these oils.

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Activity of drugs from traditional Chinese medicine toward sensitive and MDR1- or MRP1-overexpressing multidrug-resistant human CCRF-CEM leukemia cells.

Thomas Efferth, Mary Davey, Armin Olbrich … (2015)

There is considerable interest among basic and clinical researchers in novel drugs with activity against leukemia. The vast history of experience of traditional Chinese medicine (TCM) with medicinal plants may facilitate the identification of novel antileukemic compounds. In the present investigation, we tested 22 drugs for their activity toward CCRF-CEM cell lines: artesunate, artemisinin, baicalein, baicalin, berberine, bufalin, cantharidin, cephalotaxine, curcumin, daidzein, daidzin, diallyl disulfide, ginsenoside Rh2, glycyrrhizic acid, isonardosinon, homoharringtonine, nardosinon, nardofuran, puerarin, quercetin, tannic acid, and tetrahydronardosinon. As compounds from folk medicinal remedies are sometimes looked upon as alternative medicine with some hesitation or criticism, we investigated only chemically pure compounds and tested the drugs independently in two different laboratories in Germany and Australia. We used CCRF-CEM parental cells and doxorubicin-selected P-glycoprotein (P-gp)/MDR1-expressing CEM/ADR5000, vinblastine-selected P-gp/MDR1-expressing CEM/VLB(100), and epirubicin-selected multidrug resistance-related protein 1 (MRP1)-expressing CEM/E1000 sublines thereof. While CEM/ADR5000, CEM/VLB(100), and CEM/E1000 cells were highly resistant to the corresponding selecting agents, no or only minimal degrees of cross-resistance were observed to TCM drugs in both growth inhibition assay and MTT assay (range from 0.4- to 8-fold). Homoharringtonine, artesunate, and bufalin were most active among this panel of compounds. As shown by flow cytometry, artesunate significantly increased daunorubicin accumulation in CEM/E1000 cells, but not in CEM/VLB(100) or CCRF-CEM parental cells. Bufalin caused a small, but significant increase in daunorubicin accumulation in CEM/VLB(100) and CEM/E1000 cells. As artesunate and bufalin showed both antileukemic activity if applied alone and modulation activity in combination with daunorubicin in multidrug-resistant (MDR) cells, these two drugs may be suitable for novel combination treatment regimens to improve leukemia cell killing.

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Author and article information

Contributors

Thomas Efferth: efferth@uni-mainz.de

Journal

Journal ID (nlm-ta): Nat Prod Bioprospect

Journal ID (iso-abbrev): Nat Prod Bioprospect

Title: Natural Products and Bioprospecting

Publisher: Springer-Verlag (Berlin/Heidelberg )

ISSN (Print): 2192-2195

ISSN (Electronic): 2192-2209

Publication date (Electronic): 24 February 2012

Publication date PMC-release: 24 February 2012

Publication date Collection: February 2012

Volume: 2

Issue: 1

Pages: 35-40

Affiliations

[ ]Institute of Pharmacy and Molecular Biotechnology, University of Heidelberg, Heidelberg, Germany

[ ]Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Mainz, Germany

[ ]Fort McPerson, Northwest Territories, Canada

[ ]Institute of Pharmaceutical Sciences, Department Pharmacognosy, Karl-Franzens University, Graz, Austria

[ ]Wilderness International, Dresden, Germany

[ ]Stony Plain, Alberta, Canada

Article

Publisher ID: 13

DOI: 10.1007/s13659-012-0013-4

PMC ID: 4131572

SO-VID: 182c3b64-7180-43ab-980d-f7a303b3d74f

License:

Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution and reproduction in any medium, provided the original author(s) and source are credited.