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The antitumoral effect of the American mistletoe Phoradendron serotinum (Raf.) M.C. Johnst. (Viscaceae) is associated with the release of immunity-related cytokines.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE
Phoradendron serotinum is commonly used in Mexican traditional medicine for the empirical treatment of cancer. However, there are no studies regarding the antitumoral or immunomodulatory activities of Phoradendron serotinum.
MATERIALS AND METHODS
The in vivo toxicity of ethanolic extracts of Phoradendron serotinum (PSE) was evaluated in mice according to the Lorke procedure. The in vitro immunomodulatory effects of PSE were evaluated estimating the effects of PSE on the pinocytosis, NO production and lysosomal enzyme activity in murine macrophages RAW 264.7. The effects of PSE on the proliferation of murine splenocytes and NK cell activity were also assayed. The cytotoxic effects on TC-1 (lung murine cancer cells) were evaluated using the MTT assay, whereas the apoptotic effect of PSE on TC-1 cells was evaluated using TUNEL assay. Also, different doses of PSE were injected intraperitoneally daily into C57BL/6 mice bearing tumors of TC-1 cells during 25 days. The growth and weight of tumors was measured. In addition, the levels of IL-2, IL-6, IL-12, IL-23 and IFN-γ in murine serum and supernatants of K562 cell-murine splenocyte cocultures were measured.
RESULTS
PSE stimulated the proliferation, pinocytosis and lysosomal enzyme activity in murine macrophages with a similar potency than lypopolisaccharides 1 μg/ml. In addition, PSE stimulated the proliferation of murine splenocytes and induced the NK cell activity. PSE showed cytotoxic (IC(50)=1.9 μg/ml) and apoptotic effects against TC-1 cells. The LD(50) was 125 mg/kg by intraperitoneal route (i.p.) and 375 mg/kg by oral route. PSE administrated at 1, 5 and 10 mg/kg i.p. inhibited the tumor growth by 18%, 40% and 69%, respectively, in mice bearing TC-1 tumor. PSE increased the in vitro and in vivo release of IL-2, IL-6 and IFN-γ but lacked effect on IL-12 and IL-23 release.
CONCLUSIONS
Phoradendron serotinum shows moderate toxic effects in vivo, exerts cytotoxic and apoptotic effects on TC-1 cells. Phoradendron serotinum also has antitumor effects in mice bearing TC-1 tumor and induces immunomodulatory activities in vivo. The results suggest that antitumoral effects of PSE are related with the production of immunity-related cytokines.

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  • Publisher Full Text
  • Authors

    Alonso-Castro AJ, Juárez-Vázquez Mdel C, Domínguez F, González-Sánchez I, Estrada-Castillón E, López-Toledo G, Chávez M, Cerbón MA, García-Carranca A

    Institution

    Facultad de Química, Universidad Nacional Autónoma de México, México, DF, Mexico. angeljosabad@hotmail.com

    Source

    Journal of ethnopharmacology 142:3 2012 Aug 1 pg 857-64

    MeSH

    Animals
    Antineoplastic Agents, Phytogenic
    Apoptosis
    Cell Line
    Cell Line, Tumor
    Cell Proliferation
    Cytokines
    Humans
    Immunologic Factors
    K562 Cells
    Killer Cells, Natural
    Lethal Dose 50
    Lysosomes
    Macrophages
    Mice
    Mice, Inbred C57BL
    Neoplasms
    Nitric Oxide
    Phoradendron
    Plant Extracts
    Plant Leaves
    Tumor Burden

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    22732726