In cell lines derived from thyroid carcinomas, a metabolically stable form of anandamide inhibited cancer growth by stimulation of apoptosis. This growth inhibition was dependent on a high level of CB1 expression (Cozzolino et al., 2010).
Apart from inducing apoptosis, (metabolically stable) anandamide also blocks neo-vascularization in rat thyroid tumor spheroids (KiMol) and a chicken angiogenesis model (Pisanti et al., 2007).
In athymic mice with rat thyroid tumor xenografts (KiMol), elevating endocannabinoid levels by directly adding (metabolically stable) anandamide, blocking endocannabinoid reuptake or degradation inhibited tumor growth. This growth inhibition was at least partially CB1-dependent (Bifulco et al., 2001, 2004). The same (metabolically stable) anandamide also inhibited metastasis of thyroid cancer in a CB1-dependent way (Portella et al., 2003).
In the ARO cell line of the most aggressive type of thyroid cancer, anaplastic thyroid carcinoma, boosting CB2 expression dramatically increases apoptosis and sensitivity to the chemotherapeutic drug paclitaxel. Stimulating CB2 in nude mice over-expressing CB2 in thyroid cancer xenografts caused considerable tumor regression. This suggests CB2 is a therapeutic target for thyroid cancer and that CB2 expression level is an indicator of positive treatment outcome (Shi et al., 2008).
In a comparison of human benign and malignant thyroid lesions, CB1 (p<0.001) and CB2 (p<0.0005) are highly significantly overexpressed in malignant thyroid lesions. In addition, high CB2 expression is correlated to lymph node metastasis. Combined, this makes CB1 and CB2 good biomarkers for thyroid malignancy as well as therapeutic targets for the treatment of thyroid cancer (Lakiotaki et al., 2015).
In a rat thyroid cancer cell line (KiMol) several plant cannabinoids and cannabis extracts inhibited cancer cell growth although with different IC50s (Ligresti et al., 2006):
- CBD, 6.0 ± 3.0 μM
- CBD-rich extract, 6.2 ± 2.9 μM
- CBC, 7.3 ± 3.0 μM
- CBG, 8.2 ± 0.7 μM
- CBDA, 12.7 ± 3.0 μM
- THCA, 21.0 ± 2.7 μM
- THC-rich extract, 23.0 ± 2.0 μM
- THC, 23.2 ± 1.5 μM
Bifulco, M., Laezza, C., Portella, G., Vitale, M., Orlando, P., De Petrocellis, L., and Di Marzo, V. (2001). Control by the endogenous cannabinoid system of ras oncogene-dependent tumor growth. FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol. 15, 2745–2747.
Bifulco, M., Laezza, C., Valenti, M., Ligresti, A., Portella, G., and DI Marzo, V. (2004). A new strategy to block tumor growth by inhibiting endocannabinoid inactivation. FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol. 18, 1606–1608.
Cozzolino, R., Calì, G., Bifulco, M., and Laccetti, P. (2010). A metabolically stable analogue of anandamide, Met-F-AEA, inhibits human thyroid carcinoma cell lines by activation of apoptosis. Invest. New Drugs 28, 115–123.
Lakiotaki, E., Giaginis, C., Tolia, M., Alexandrou, P., Delladetsima, I., Giannopoulou, I., Kyrgias, G., Patsouris, E., and Theocharis, S. (2015). Clinical Significance of cannabinoid Receptors CB1 and CB2 Expression in Human Malignant and Benign Thyroid Lesions. BioMed Res. Int. 2015, 839403.
Ligresti, A., Moriello, A.S., Starowicz, K., Matias, I., Pisanti, S., Petrocellis, L.D., Laezza, C., Portella, G., Bifulco, M., and Marzo, V.D. (2006). Antitumor Activity of Plant cannabinoids with Emphasis on the Effect of Cannabidiol on Human Breast Carcinoma. J. Pharmacol. Exp. Ther. 318, 1375–1387.
Pisanti, S., Borselli, C., Oliviero, O., Laezza, C., Gazzerro, P., and Bifulco, M. (2007). Antiangiogenic activity of the endocannabinoid anandamide: correlation to its tumor-suppressor efficacy. J. Cell. Physiol. 211, 495–503.
Portella, G., Laezza, C., Laccetti, P., De Petrocellis, L., Di Marzo, V., and Bifulco, M. (2003). Inhibitory effects of cannabinoid CB1 receptor stimulation on tumor growth and metastatic spreading: actions on signals involved in angiogenesis and metastasis. FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol. 17, 1771–1773.
Shi, Y., Zou, M., Baitei, E.Y., Alzahrani, A.S., Parhar, R.S., Al-Makhalafi, Z., and Al-Mohanna, F.A. (2008). cannabinoid 2 receptor induction by IL-12 and its potential as a therapeutic target for the treatment of anaplastic thyroid carcinoma. cancer Gene Ther. 15, 101–107.