Melanoma is responsible for 0.6% of global cancer deaths, and is the leading cause of skin cancer deaths. New research is emerging that may advance the treatment strategy. Depending on the location and severity of skin cancer, the treatment may range from excision, selective lymphadenectomy (the removal of lymph nodes if metastasis has occurred), and possibly immunotherapy (trying to improve the immune system to fight the cancer). While the first two treatments remain effective, improved immunotherapy treatments using terpenoids were explored by the Department of Biochemistry and Medical Chemistry at The Pomeranian Medical University in Szczecin. Their findings were released in a new study, and may lead to improved treatment strategies. [1]
Traditional Melanoma Immunotherapy Treatment
Thus far, there are three antibody treatments approved for melanoma. These treatments improve the response of T-cells, a type of white blood cell. In more severe cases, the Food & Drug Administration has approved a modified herpes virus called talimogene laherparepvec (T-VEC) to act as a melanoma vaccine and with specific cases, standard chemotherapy may be employed. Chemotherapy is often reserved only for well-defined cases with advanced tumor development, though, as there is typically a low level of response for melanoma patients. Even with these standard treatments, melanoma remains a difficult cancer to treat due to its broad range of tumor development and its flexibility in adaptation.
Using Plant-Based Terpenes as a Treatment Method
Terpenes and terpenoids (terpenes containing other atoms besides carbon and hydrogen such as oxygen) are plant-based compounds that provide a wide variety of functions. In plants, they can signal everything from temperature changes to fighting pathogens and herbivores. For medical uses, terpenes have been shown to be antibacterial, antifungal, anti-inflammatory, and, most importantly, anticancer. By combining terpenes with traditional treatments for melanoma, different results emerged and have proved effective at combating the disease at different stages of development.
Effective Monoterpenoid Treatments
Monoterpenoids are the simplest form of terpenes that are made up of a single carbon isoprenoid unit. Several monoterpenoids have proven effective in treating breast, lung, gastric, colon, prostate, ovarian, liver, cervical, head, neck, and skin cancers as well as leukemia. This is especially true when combined with traditional treatment measures. For example, thymoquinone (TQ), a component of black seed, indicated positive longevity results when treating mice with metastasized melanoma. [2] A combination of TQ with stereotactic radiosurgery also led to increased survival, but the effects of the combination did not outperform radiosurgery alone.
Terpineols, terpenoid alcohols commonly found in oregano and basil, have anticancer [3] and antibacterial [4] properties. When using 500 µg/mL doses, one study found that α-terpineol encapsulated within polymer nanoparticles decreased the viability of a human skin cancer cell line by 59%. [5]
Borneol is another monoterpenoid that has the added benefit of loosening cell wall restriction to allow higher permeation of medication. [6] It also enhances the effectiveness of chemotherapy drugs. [7]
Finally, camphene, which can be found in conifers, rosemary, hemp, pepper and nutmeg, has been shown to increase cytosolic calcium levels and mitotoxic effects, leading to an overall decrease in tumor volume in mice. [8]
These are just a few of the monoterpenoids the review paper highlights, as citral, limonene, and linalool also demonstrated anticancer properties.
Sesquiterpenoids in Cancer Treatment
Similar in structure but more chemically complex, sesquiterpenoids also have shown positive signs in cancer treatment. β-Elemene, found in a Chinese medical plant similar to ginger as well as celery and mint, led to more effective cancer cell death and limited cell migration, invasion, and expression of metastasis proteins when compared to immunotherapy alone. [9] β-Caryophyllene, found in cloves, black pepper, cinnamon, thyme, oregano, and cannabis, likewise has shown signs of improved apoptosis and limiting tumor growth by suppressing angiogenesis and lymphangiogenesis in cancer cells. [10]
These studies highlight how mono- and sesquiterpenoids have demonstrated promise in treating melanoma. In an upcoming blog, we will canvas the anticancer potential of di- and triterpenoids.
References
[1] Kłos P, Chlubek D. Plant-derived terpenoids: A promising tool in the fight against melanoma. Cancers (Basel). 2022;14(3):502. [journal impact factor = 6.639; times cited = 0][2] Hatiboglu MA, Kocyigit A, Guler EM, et al. Thymoquinone induces apoptosis in B16-F10 melanoma cell through inhibition of p-STAT3 and inhibits tumor growth in a murine intracerebral melanoma model. World Neurosurg. 2018;114:e182-e190. [journal impact factor = 2.104; times cited = 22]
[3] Negreiros HA, de Moura KG, Barreto do Nascimento MLL, et al. Alpha-terpineol as antitumor candidate in pre-clinical studies. Anticancer Agents Med Chem. 2021;21(15):2023-2031. [journal impact factor = 2.505; times cited = 2]
[4] Khaleel C, Tabanca N, & Buchbauer G. α-Terpineol, a natural monoterpene: A review of its biological properties. Open Chemistry. 2018;16(1):349-361. [journal impact factor = 1.554; times cited = 89]
[5] Alves Batista F, Brena Cunha Fontele S, Beserra Santos LK, Alves Filgueiras L, Quaresma Nascimento S, et al. Synthesis, characterization of α-terpineol-loaded PMMA nanoparticles as proposed of therapy for melanoma. Materials Today Communications. 2020;22: 100762. [journal impact factor = 3.383; times cited = 18]
[6] Wang Z, Li Q, Xia L, et al. Borneol promotes apoptosis of human glioma cells through regulating HIF-1a expression via mTORC1/eIF4E pathway. J Cancer. 2020;11(16):4810-4822. [journal impact factor = 4.207; times cited = 6]
[7] Meng X, Dong X, Wang W, et al. Natural borneol enhances paclitaxel-induced apoptosis of ESCC cells by inactivation of the PI3K/AKT. J Food Sci. 2018;83(5):1436-1443. [journal impact factor = 3.167; times cited = 10]
[8] Girola N, Figueiredo CR, Farias CF, et al. Camphene isolated from essential oil of Piper cernuum (Piperaceae) induces intrinsic apoptosis in melanoma cells and displays antitumor activity in vivo. Biochem Biophys Res Commun. 2015;467(4):928-934. [journal impact factor = 3.575; times cited = 55]
[9] Shi H, Liu L, Liu L, Geng J, Zhou Y, Chen L. β-Elemene inhibits the metastasis of B16F10 melanoma cells by downregulation of the expression of uPA, uPAR, MMP-2, and MMP-9. Melanoma Res. 2014;24(2):99-107. [journal impact factor = 3.599; times cited = 19]
[10] Jung JI, Kim EJ, Kwon GT, et al. β-Caryophyllene potently inhibits solid tumor growth and lymph node metastasis of B16F10 melanoma cells in high-fat diet-induced obese C57BL/6N mice. Carcinogenesis. 2015;36(9):1028-1039. [journal impact factor = 4.944; times cited = 32]
Credit: Photo by Agnieszka Kowalczyk on Unsplash
