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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.