8.13 Melanoma and Other Skin Cancers


Killing Cancer Cells

CBD and THC induce apoptosis by different mechanisms in melanoma cells, and THC + CBD in a 1/1 ratio is even more effective against melanoma in both in vitro experiments and animal studies[Armstrong_2015]. CBG exhibits significant inhibitory activity against mouse skin melanoma cells[Baek_1996].

Linalool and β-caryophyllene are cytotoxic against human melanoma cells[Tundis_2009]. 4-Terpineol is cytotoxic against murine melanoma cells, including drug-resistant cells[Greay_2009]. γ-Terpinene is cytotoxic against mouse melanoma cells[Ferraz_2013],

α-Pinene, used as the main component of a fragrant environment has reduced melanoma tumor size in mice by about 40%. However, the same effect was not observed in an in vitro experiment, suggesting that the effect of the fragrant environment was indirect[Kusuhara_2012].

α-humulene kills human melanoma cells[Legault_2003]. 

Halting Cell Division

4-Terpineol induces cell-cycle arrest in murine mesothelioma and B16 melanoma[Greay_2009].  

Controlling Cytokines

IL-1β, IFN-γ and CXCL10 are significantly increased in advanced melanoma patients[Jiang_2014]. IL-8 is essential for cancer growth[Schadendorf_1993].

In a mouse model, IL1-β was required for tumor invasiveness and angiogenesis[Voronov_2003]. Interestingly, a blockade of IL-1 inhibited melanoma metastasis to some locations but not others. Metastases to bone marrow, spleen, liver, lung, pancreas, skeletal muscle, adrenal gland, and heart were inhibited by  IL-1 blockade, but metastases to kidney, testis, brain, skin, and gastrointestinal tract were not[Anasagasti_1997],

In a mouse model of melanoma, IL-23 stimulated production of IL-17, which stimulated production of IL-6, which stimulated tumor growth. lowering any of these cytokines led to a reduction of tumor growth[Tang_2013].


Armstrong_2015. Exploiting Cannabinoid-Induced Cytotoxic Autophagy to Drive Melanoma Cell Death. Full text. Armstrong J L, Hill D S, McKee C S, et al. Journal of investigative dermatology. Published 2015 June 1.

Baek_1996. Synthesis and antitumor activity of cannabigerol. Abstract. Baek S-H, Du Han S, Yook C N, et al. Archives of Pharmacal Research. Published June 1996.

Tundis_2009. In vitro cytotoxic effects of Senecio stabianus Lacaita (Asteraceae) on human cancer cell lines. Abstract. Tundis R, Loizzo M R, Marco Bonesi M, et al. Natural product research. 2009.

Greay_2009. Induction of necrosis and cell cycle arrest in murine cancer cell lines by Melaleuca alternifolia (tea tree) oil and terpinen-4-ol. Abstract. Greay S J, Ireland D J, Kissick H T, et al. Cancer chemotherapy and pharmacology. Online 2009 August 13.

Ferraz_2013. Cytotoxic effect of leaf essential oil of Lippia gracilis Schauer (Verbenaceae). Abstract. Ferraz P C R, Bomfim D S, Carvalho N C, et al. Phytomedicine. 2013 May 15.

Kusuhara_2012. Fragrant environment with α-pinene decreases tumor growth in mice. Abstract, full text. Kusuhara M, Urakami U, Masuda Y, et al. Biomedical Research. Published 2012. 

Legault_2003. Antitumor activity of balsam fir oil: production of reactive oxygen species induced by alpha-humulene as possible mechanism of action. Abstract. Legault J, Dahl W, Debiton E, et al. Planta medica. 2003 May.

Jiang_2014. Elevated chronic inflammatory factors and myeloid-derived suppressor cells indicate poor prognosis in advanced melanoma patients. Full text. Jiang H, Gebhardt C, Umansky L, et al. International Journal of Cancer. Online 2014 October 29. 

Schadendorf_1993. IL-8 produced by human malignant melanoma cells in vitro is an essential autocrine growth factor. Abstract.
Schadendorf D, Möller A, Algermissen B, et al. The Journal of immunology. Published 1993 September 1.

Voronov_2003. IL-1 is required for tumor invasiveness and angiogenesis. Full text. Voronov E, Shouval D S, Krelin Y, et al. Proceedings of the National Academy of Sciences (U.S.). Online 2003 March 4.

Anasagasti_1997. Interleukin 1-dependent and -independent mouse melanoma metastases. Abstract. Anasagasti M J, Olaso E, Calvo F, et al. Journal of the National Cancer Institute. Published 1997 May 7.

Tang_2013. Hmgb1-IL-23-IL-17-IL-6-Stat3 Axis Promotes Tumor Growth in Murine Models of Melanoma. Full text. Tang Q, Li J, Zhu H, et al. Mediators of inflammation. 2013 December 28.