Essential Oils and Their Main Chemical Components: The Past 20 Years of Preclinical Studies in Melanoma

Abstract

The last two decades have seen the development of effective therapies, which have saved the lives of a large number of melanoma patients. However, therapeutic options are still limited for patients without BRAF mutations or in relapse from current treatments, and severe side effects often occur during therapy. Thus, additional insights to improve treatment efficacy with the aim to decrease the likelihood of chemoresistance, as well as reducing side effects of current therapies, are required. Natural products offer great opportunities for the discovery of antineoplastic drugs, and still represent a useful source of novel molecules. Among them, essential oils, representing the volatile fraction of aromatic plants, are always being actively investigated by several research groups and show promising biological activities for their use as complementary or alternative medicine for several diseases, including cancer. In this review, we focused on studies reporting the mechanism through which essential oils exert antitumor action in preclinical wild type or mutant BRAF melanoma models. We also discussed the latest use of essential oils in improving cancer patients' quality of life. As evidenced by the many studies listed in this review, through their effect on apoptosis and tumor progression-associated properties, essential oils can therefore be considered as potential natural pharmaceutical resources for cancer management.

Keywords: angiogenesis; apoptosis; essential oils; melanoma; metastasis.

Figure 1

EOs and their components reduce tumor angiogenesis, lymphangiogenesis (A) and tumor metastasization, by targeting proteins responsible for tumor dissemination (B) and tumor-promoting inflammation (C). Angiopoietin 2 (ANGPT2), vascular endothelial growth factor (VEGF), hypoxia responsive factor 1α (HIF-1α), lymphatic vessel endothelial receptor (LYVE-1), cluster of differentiation 31 (CD31), cluster of differentiation 34 (CD34), vascular endothelial cadherin (VE-cadherin), fibroblast growth factor 2 (FGF-2), phospho vascular endothelial growth factor receptor 2 (pVEGFR2), phospho fibroblast growth factor receptor-1 (pFGFR1), krüppel-like factor 4 (KFL4), programmed death-ligand 1 (PD-L1), tissue inhibitor of metalloproteinase-1 (TIMP-1) and -2 (TIMP-2), extracellular signal-regulated kinase-1 (ERK-1) and -2 (ERK-2), focal adhesion kinase (FAK), growth factor receptor-bound protein 2 (Grb2), urokinase-type plasminogen activator (uPA), uPA receptor (uPAR), metalloproteinases-2 (MMP-2) and -9 (MMP-9), nuclear factor kappa B (NF-kB), NLR family pyrin domain containing 3 (NLRP3), interleukin 1β (IL-1 β), interleukin 6 (IL-6), interleukin 2 (IL-2), tumor necrosis factor-α (TNF-α), transforming growth factor β1 (TGF-β1), macrophage colony stimulating factor (M-CSF), granulocyte-macrophage colony stimulating factor (GM-CSF), monocyte chemoattractant protein-1 (MCP-1), keratinocyte chemoattractant (KC). Proteins that are upregulated by EOs or their components are reported in green, proteins that are downregulated by EOs or their components are reported in red. Parts of the figure are drawn using pictures from Servier Medical Art (https://smart.servier.com).

Figure 2

EOs and their components reduce melanogenesis and oxidation through interconnected mechanisms. Superoxide dismutase (SOD), glutathione peroxidase (GPX), catalase (CAT), glutathione (GSH), reactive oxygen species (ROS), α-melanocyte stimulating hormone (α-MSH), melanocortin 1 receptor (MC1R), adenylyl cyclase (AC), stem cell factor (SCF), microphthalmia-associated transcription factor (MITF), tyrosinase (TYR), tyrosinase-related protein -1 (TRP-1) and -2 (TRP-2), glycogen synthase kinase 3β (GSK3β), c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK). Proteins that are upregulated by EOs or their components are reported in green, proteins that are downregulated by EOs or their components are reported in red. Parts of the figure are drawn using pictures from Servier Medical Art (https://smart.servier.com).