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.
Links
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 857-64MeSH
AnimalsAntineoplastic 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 ArticleResearch Support, Non-U.S. Gov't
Language
eng
PubMed ID
22732726
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