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Cannabinoid 2 receptor induction by IL-12 and its potential as a therapeutic target for the treatment of anaplastic thyroid carcinoma.

Abstract

Anaplastic thyroid carcinoma is the most aggressive type of thyroid malignancies. Previously, we demonstrated that tumorigenicity of anaplastic thyroid carcinoma cell line ARO was significantly reduced following interleukin (IL)-12 gene transfer. We suspected that tumor target structure in ARO/IL-12 cells might be changed and such a change may make them more susceptible to be killed through mechanisms apart from natural killer-dependent pathway. To identify genes involved, we examined gene expression profile of ARO and ARO/IL-12 by microarray analysis of 3757 genes. The most highly expressed gene was cannabinoid receptor 2 (CB2), which was expressed eightfold higher in ARO/IL-12 cells than ARO cells. CB2 agonist JWH133 and mixed CB1/CB2 agonist WIN-55,212-2 could induce significantly higher rate of apoptosis in ARO/IL-12 than ARO cells. Similar results were obtained when ARO cells were transfected with CB2 transgene (ARO/CB2). A considerable regression of thyroid tumors generated by inoculation of ARO/CB2 cells was observed in nude mice following local administration of JWH133. We also demonstrated significant increase in the induction of apoptosis in ARO/IL12 and ARO/CB2 cells following incubation with 15 nM paclitaxel, indicating that tumor cells were sensitized to chemotherapy. These data suggest that CB2 overexpression may contribute to the regression of human anaplastic thyroid tumor in nude mice following IL-12 gene transfer. Given that cannabinoids have shown antitumor effects in many types of cancer models, CB2 may be a viable therapeutic target for the treatment of anaplastic thyroid carcinoma.

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  • Publisher Full Text
  • Authors+Show Affiliations

    ,

    Department of Genetics, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia. yufei@kfshrc.edu.sa

    , , , , ,

    Source

    Cancer gene therapy 15:2 2008 Feb pg 101-7

    MeSH

    Animals
    Apoptosis
    Carcinoma
    Cell Line, Tumor
    Female
    Gene Transfer Techniques
    Genetic Therapy
    Humans
    Interleukin-12
    Mice
    Mice, Inbred BALB C
    Mice, Nude
    Neoplasm Transplantation
    Receptor, Cannabinoid, CB2
    Thyroid Neoplasms

    Pub Type(s)

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

    Language

    eng

    PubMed ID

    18197164

    Citation

    TY - JOUR T1 - Cannabinoid 2 receptor induction by IL-12 and its potential as a therapeutic target for the treatment of anaplastic thyroid carcinoma. AU - Shi,Y, AU - Zou,M, AU - Baitei,E Y, AU - Alzahrani,A S, AU - Parhar,R S, AU - Al-Makhalafi,Z, AU - Al-Mohanna,F A, Y1 - 2007/12/21/ PY - 2007/12/21/aheadofprint PY - 2008/1/17/pubmed PY - 2008/2/20/medline PY - 2008/1/17/entrez SP - 101 EP - 7 JF - Cancer gene therapy JO - Cancer Gene Ther. VL - 15 IS - 2 N2 - Anaplastic thyroid carcinoma is the most aggressive type of thyroid malignancies. Previously, we demonstrated that tumorigenicity of anaplastic thyroid carcinoma cell line ARO was significantly reduced following interleukin (IL)-12 gene transfer. We suspected that tumor target structure in ARO/IL-12 cells might be changed and such a change may make them more susceptible to be killed through mechanisms apart from natural killer-dependent pathway. To identify genes involved, we examined gene expression profile of ARO and ARO/IL-12 by microarray analysis of 3757 genes. The most highly expressed gene was cannabinoid receptor 2 (CB2), which was expressed eightfold higher in ARO/IL-12 cells than ARO cells. CB2 agonist JWH133 and mixed CB1/CB2 agonist WIN-55,212-2 could induce significantly higher rate of apoptosis in ARO/IL-12 than ARO cells. Similar results were obtained when ARO cells were transfected with CB2 transgene (ARO/CB2). A considerable regression of thyroid tumors generated by inoculation of ARO/CB2 cells was observed in nude mice following local administration of JWH133. We also demonstrated significant increase in the induction of apoptosis in ARO/IL12 and ARO/CB2 cells following incubation with 15 nM paclitaxel, indicating that tumor cells were sensitized to chemotherapy. These data suggest that CB2 overexpression may contribute to the regression of human anaplastic thyroid tumor in nude mice following IL-12 gene transfer. Given that cannabinoids have shown antitumor effects in many types of cancer models, CB2 may be a viable therapeutic target for the treatment of anaplastic thyroid carcinoma. SN - 1476-5500 UR - https://www.unboundmedicine.com/medline/citation/18197164/full_citation/Cannabinoid_2_receptor_induction_by_IL_12_and_its_potential_as_a_therapeutic_target_for_the_treatment_of_anaplastic_thyroid_carcinoma_ L2 - http://dx.doi.org/10.1038/sj.cgt.7701101 ER -