title: Evaluation of anti-cancer and immunomodulatory effects of carnosol in a Balb/c WEHI-164 fibrosarcoma model.
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.
authors.affiliation: Immunology Research Center, Bu-Ali Research Institute, Mashhad University of Medical Sciences , Mashhad , Iran .
authors.forename: Maryam
authors.initials: M
authors.lastname: Rahnama
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Mahmoudi
authors.forename: Shahrzad
authors.initials: S
authors.lastname: Zamani Taghizadeh Rabe
authors.forename: Mahdi
authors.initials: M
authors.lastname: Balali-Mood
authors.forename: Gholamreza
authors.initials: G
authors.lastname: Karimi
authors.forename: Nafiseh
authors.initials: N
authors.lastname: Tabasi
authors.forename: Bamdad
authors.initials: B
authors.lastname: Riahi-Zanjani
mesh_terms: D045784:Abietanes / Q000008:administration & dosage*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism; D005354:Fibrosarcoma / Q000188:drug therapy*; D006801:Humans; D056747:Immunomodulation; D007274:Injections, Intraperitoneal; D008213:Lymphocyte Activation / Q000187:drug effects; D016246:Lymphocytes, Tumor-Infiltrating / Q000187:drug effects* / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D027542:Rosmarinus; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D045784:Abietanes; D000970:Antineoplastic Agents; D016207:Cytokines; C068623:carnosol
keywords: Anti-tumor; Balb/c; carnosol; regulatory T-cell