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

Mol Carcinog. 2019 May;58(5):722-734. doi: 10.1002/mc.22965. Epub 2019 Jan 20.


Bioactive derivatives from the camphor laurel tree, Cinnamomum camphora, are posited to exhibit chemopreventive properties but the efficacy and mechanism of these natural products are not fully understood. 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 identified by RNA-sequencing, 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 a mechanism through which a plant-derived essential oil diminishes established tumor burden.

Keywords: NFAT; calcium; camphor white oil; inflammation; squamous cell carcinoma.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Anthracenes / toxicity
  • Camphor / administration & dosage*
  • Carcinoma, Squamous Cell / chemically induced
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / immunology
  • Cell Proliferation
  • Cells, Cultured
  • Female
  • Humans
  • Keratinocytes / drug effects*
  • Keratinocytes / immunology
  • Keratinocytes / pathology
  • Mice
  • NFATC Transcription Factors / metabolism
  • Oils, Volatile / administration & dosage*
  • Piperidines / toxicity
  • Skin Neoplasms / chemically induced
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / immunology
  • T-Lymphocytes, Cytotoxic / drug effects
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / metabolism


  • 3-(2,6-bis(4-fluorophenyl)-3-methylpiperidin-4-ylideneamino)-2-thioxoimidazolidin-4-one on 7,12-dimethylbenz(a)anthracene
  • Anthracenes
  • NFATC Transcription Factors
  • Oils, Volatile
  • Piperidines
  • Camphor