To date, over 200 terpenes have been identified in various cannabis chemovars. [1] These molecules are responsible for cannabis’ characteristic aroma, and together with other plant phytochemicals, they contribute to cannabis’ therapeutic benefits.
Difficulties of terpene identification are linked to their relatively low abundance in cannabis flowers, high thermolability and volatility, content variations within cannabis varieties, and uncertainty related to their stereochemical structure. [1] Terpenes commonly found in cannabis cultivars include myrcene, β-caryophyllene, α-humulene, α-pinene, limonene, etc.
In addition to their antiviral, antiplasmodial, antinflammatory, antifungal, analgesic, and antimicrobial medicinal properties [2], terpenes have attained great attention for their ability to selectively kill tumor cells in vivo and in vitro, in addition to their capability to suppress carcinogenic growth in preclinical animal models [1].
Among lesser-known terpenes present in certain cannabis varieties, eucalyptol induces dose-dependent apoptosis in leukemia cells and other human cancer cell lines. [1] Eucalyptol is the main constituent of eucalyptus oil and is found also in rosemary, sage, and wormwood plants. This monoterpenoid with its fresh and mint-like smells reduced tumor progression in immunodeficient mice transplanted with human colon cancer cells in comparison to a control group. [3]
Borneol is a terpenoid found in cannabis as well as ginger, rosemary, camphor, and thyme. This compound has the similar fresh camphor-like scent of eucalyptol with earthy tones. Borneol was shown to act synergistically with antitumor drugs enhancing their action in chemotherapeutic resistant cancer cells. [4,5] Plants containing this compound have been used in traditional Chinese medicine to improve drug absorption. It has been reported that borneol can induce blood-brain barrier transient disruption: this capability has been exploited to create various drug formulations targeting cancer cells in the brain and enhancing anti-cancer efficiency of various chemotherapeutic drugs. [6]
The sesquiterpene valencene has shown cytotoxic and anti-tumor activity against ovarian and lymphoblast cancer cell lines. [7] This compound has a citrus-like aroma and is usually found in grapefruits, nectarines, mangoes, and tangerines. Valencene is capable of acting synergistically with the chemotherapy medication doxorubicin to inhibit the proliferation of colorectal adenocarcinoma cell lines. [8]
The cyclic monoterpene α-phellandrene has been shown to induce alterations in gene expression displaying anticancer effects: administration of α-phellandrene induced dose and time-dependent autophagy in human liver cancer cells, suppressing tumorogenesis by inhibiting cancer cell survival and inducing cell death. [9] [1]
More biological studies have to be performed to fully exploit the beneficial effects of terpenes in the battle against cancer.
References
[1] Tomko AM, et al. Anti-cancer potential of cannabinoids, terpenes, and flavonoids present in cannabis. Cancers. 2020;12(7):1985. doi:10.3390/cancers12071985[Journal Impact Factor = 6.639] [Times cited = 14 (Semantic Scholar)]
[2] Cox-Georgian D, et al. Therapeutic and medicinal uses of terpenes. Medicinal Plants. 2019:333–359. doi: 10.1007/978-3-030-31269-5_15 [Times cited = 27 (Semantic Scholar)]
[3] Murata S, et al. Antitumor effect of 1,8-cineole against colon cancer. Oncol Rep. 2013;30:2647–2652. [Journal Impact Factor = 3.906] [Times cited = 77 (Semantic Scholar)]
[4] Meng X, et al. Natural borneol enhances paclitaxel-induced apoptosis of ESCC cells by inactivation of the PI3K/AKT. J Food Sci. 2018;83:1436–1443. [Journal Impact Factor = 3.167] [Times cited = 7 (Semantic Scholar)]
[5] Su J, et al. Natural borneol, a monoterpenoid compound, potentiates selenocystine-induced apoptosis in human hepatocellular carcinoma cells by enhancement of cellular uptake and activation of ROS-mediated DNA damage. PLoS ONE. 2013;8(e63502). [Journal Impact Factor = 3.240] [Times cited = 59 (Semantic Scholar)]
[6] Yin Y, et al. L-Borneol induces transient opening of the blood–brain barrier and enhances the therapeutic effect of cisplatin. NeuroReport. 2017;28:506–513. [Journal Impact Factor = 1.837] [Times cited = 22 (Semantic Scholar)]
[7] Ambrož M, et al. The effects of selected sesquiterpenes from Myrica rubra essential oil on the efficacy of doxorubicin in sensitive and resistant cancer cell lines. Molecules. 2017;22(6):1021. [Journal Impact Factor = 4.411] [Times cited = 12 (Semantic Scholar)]
[8] Ambrož M, et al. The influence of sesquiterpenes from Myrica rubra on the antiproliferative and pro-oxidative effects of doxorubicin and its accumulation in cancer cells. Molecules. 2015;20:15343–15358. [Journal Impact Factor = 4.411] [Times cited = 31 (Semantic Scholar)]
[9] Hsieh S-L, et al. Induction of necrosis in human liver tumor cells by α-phellandrene. Nutr Cancer. 2014; 66:970–979. [Journal Impact Factor = 2.615] [Times cited = 7 (Semantic Scholar)]
Image: National Cancer Institute, Unsplash
