Evaluation of anti-cancer and immunomodulatory effects of carnosol in a Balb/c WEHI-164 fibrosarcoma model

Rahnama, M. and Mahmoudi, M. and Zamani Taghizadeh Rabe, S. and Balali-Mood, M. and Karimi, G. and Tabasi, N. and Riahi-Zanjani, B. (2015) Evaluation of anti-cancer and immunomodulatory effects of carnosol in a Balb/c WEHI-164 fibrosarcoma model. Journal of Immunotoxicology, 12 (3). pp. 231-238.

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Abstract

Agents that destroy tumor cells and simultaneously boost host anti-tumor immunity are of keen interest in cancer therapy. In the present study, the effect of carnosol on anti-tumor immunity in a Balb/c mouse model of fibrosarcoma was evaluated. Carnosol was administered intraperitoneally daily (at 5 or 10 mg/kg/day, for 7 days) to tumor-bearing mice (i.e. 7 days after initial injection of tumor cells). Another group of tumor-bearing mice was treated with 20 mg cyclophosphamide/kg/d (positive control); a final group received vehicle only (vehicle control). After an initial measure on Day 0, tumor size was measured twice during the 7-day treatment period. One day after the final treatment with vehicle/carnosol (i.e. Day 7), the mice had their tumors measured and then were euthanized to permit their spleen and tumor to be harvested for isolation of, respectively, splenocytes and tumor-associated lymphocytes. Using these materials, spontaneous and mitogen-induced release of interleukin (IL)-4, IL-10, and interferon (IFN)-γ, lymphocyte proliferation, and the absolute numbers/relative percentages of splenic and tumor-associated T-regulatory (Treg) and other T-lymphocyte sub-sets were evaluated. The results showed that carnosol at both doses significantly suppressed tumor growth and caused depletion of splenic and tumor-associated Treg cells. It also caused relative (vs control mouse cell values) decreases in splenocyte spontaneous/inducible production of IL-4 and IL-10 and increases in IFNγ and cell proliferation. Carnosol at either dose did not cause changes in the percentages of CD4+ or CD8+ lymphocytes in the spleen or in tumor-associated lymphocyte populations. The observed increases in IFNγ, decreases in IL-10 and IL-4 production, and reductions in splenic/tumor-associated Treg cell levels might be signs reflecting the potential anti-tumor activity of carnosol. Based on the findings here, it is asserted that carnosol is a likely candidate-after more complete toxicologic evaluation-for eventual use as an anti-cancer therapeutic. © 2014 Informa Healthcare USA, Inc. All rights reserved: reproduction in whole or part not permitted.

Item Type: Article
Additional Information: Cited By :9 Export Date: 16 February 2020 Correspondence Address: Riahi-Zanjani, B.; Medical Toxicology Research Center, School of Medicine, Mashhad University of Medical SciencesIran
Uncontrolled Keywords: Anti-tumor Balb/c Carnosol Regulatory T-cell antineoplastic agent CD4 antigen cyclophosphamide gamma interferon immunomodulating agent interleukin 10 interleukin 2 receptor alpha interleukin 4 transcription factor FOXP3 abietane derivative cytokine animal cell animal experiment animal model animal tissue antineoplastic activity Article CD4+ T lymphocyte CD8+ T lymphocyte controlled study cytokine production cytokine release fibrosarcoma immunomodulation lymphocyte count lymphocyte proliferation male mononuclear cell mouse nonhuman priority journal regulatory T lymphocyte spleen spleen cell T lymphocyte subpopulation treatment duration tumor associated leukocyte tumor growth tumor immunity tumor volume animal Bagg albino mouse cell growth drug effects human immunology intraperitoneal drug administration lymphocyte activation metabolism Neoplasms, Experimental Rosmarinus tumor cell line Mus Animals Antineoplastic Agents Cell Growth Processes Cell Line, Tumor Cytokines Diterpenes, Abietane Humans Injections, Intraperitoneal Lymphocytes, Tumor-Infiltrating Mice Mice, Inbred BALB C T-Lymphocyte Subsets T-Lymphocytes, Regulatory Tumor Burden
Subjects: QV pharmacology
QZ pathology-neoplasms-Genetics
Divisions: Mashhad University of Medical Sciences
Depositing User: mr lib5 lib5
Date Deposited: 25 Apr 2020 08:23
Last Modified: 25 Apr 2020 08:23
URI: http://eprints.mums.ac.ir/id/eprint/16532

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