Anticancer Properties of Essential Oils and Other Natural Products

Abstract

Essential oils are secondary metabolites with a key-role in plants protection, consisting primarily of terpenes with a volatile nature and a diverse array of chemical structures. Essential oils exhibit a wide range of bioactivities, especially antimicrobial activity, and have long been utilized for treating various human ailments and diseases. Cancer cell prevention and cytotoxicity are exhibited through a wide range of mechanisms of action, with more recent research focusing on synergistic and antagonistic activity between specific essential oils major and minor components. Essential oils have been shown to possess cancer cell targeting activity and are able to increase the efficacy of commonly used chemotherapy drugs including paclitaxel and docetaxel, having also shown proimmune functions when administered to the cancer patient. The present review represents a state-of-the-art review of the research behind the application of EOs as anticancer agents both in vitro and in vivo. Cancer cell target specificity and the use of EOs in combination with conventional chemotherapeutic strategies are also explored.

Figure 1

Chemical structures of essential oil constituents.

Figure 2

Essential oils cancer preventative and anticancer mechanisms of action. EOs possess antimutagenic, antiproliferative, antioxidant, and detoxifying capabilities acting on various pathways in the cancer cell as well as cancer preventative capabilities. EOs may directly inhibit mutagen entry into the cell. EOs can decrease phase I enzymes such as CytC, preventing mutagen formation, and increase phase II enzymes such as GST, UGT, QR, and EH for enhanced detoxification. EOs bind ROS forming reactive phenoxy radicals which bind further ROS and increase antioxidative enzymes CAT, SOD, GPx, and GSH thus preventing oxidative damage as a cancer preventative mechanism. EOs disrupt mitochondrial membrane potential causing an increase in ROS and decrease in GSH, release of CytC, resulting in a cascade of disruption in Bcl/Bax ratio, increase in caspase 3 and caspase 9 activity, and PARP cleavage, resulting in apoptosis. EOs suppress mTOR and pPDK1 causing PKB dephosphorylation, which dually acts to initiate caspase activity and deactivate mdm2, causing an increase in p21 to further initiate caspase activity resulting in apoptosis. Increased p21 also induces G1/S phase cell cycle arrest. EOs cause a decrease in CDK7, blocking CDK1/cyclin complex causing G2/M phase cell cycle arrest. Bax: B-cell lymphoma 2-associated X protein; Bcl-2: B-cell lymphoma 2; CAT: catalase; CDK: cyclin-dependant kinase; CytC: cytochrome C; CytP450: cytochrome P450; EH: epoxide hydrolase; EO: essential oil; ER: endoplasmic reticulum; ETC: electron transport chain; GPx: glutathione peroxidase; GSH: glutathione; GST: glutathione S-transferase; mdm2: murine double minute 2; mTOR: mechanistic target of rapamycin; MITO: mitochondria; NFκB: nuclear factor-κB; PARP: poly ADP ribose polymerase; pPDK1: protein pyruvate dehydrogenase kinase 1; PKB: protein kinase B; QT: quinone reductase; ROS: reactive oxygen species; SOD: superoxide dismutase; UGT: uridine 5′-diphospho-glucuronosyltransferase.