Camphor white oil induces tumor regression through cytotoxic T cell-dependent mechanisms

Bioactive derivatives from the camphor laurel tree, Cinnamomum camphora , are posited to exhibit chemopreventive properties but the efficacy and mechanism of these natural products have not been established. We tested an essential-oil derivative, camphor white oil (CWO), for anti-tumor activity in a mouse model of keratinocyte-derived skin cancer. Daily topical treatment with CWO induced dramatic regression of pre-malignant skin tumors and a two-fold reduction in cutaneous squamous cell carcinomas. We next investigated underlying cellular and molecular mechanisms. In cultured keratinocytes, CWO stimulated calcium signaling, resulting in calcineurin-dependent activation of nuclear factor of activated T cells (NFAT). In vivo , CWO induced transcriptional changes in immune-related genes, resulting in cytotoxic T cell-dependent tumor regression. Finally, we identified chemical constituents of CWO that recapitulated effects of the admixture. Together, these studies identify T cell-mediated tumor regression as the mechanism through which a plant-derived essential oil diminishes established tumor burden. SUMMARY BLURB Essential oil derived from the camphor tree acts by stimulating immune cell-dependent regression of skin tumors in a mouse model of cutaneous squamous cell carcinoma.