Molecular insights on chemopreventive and anticancer potential of carvacrol: Implications from solid carcinomas

Abstract

Globally, cancer is one of the deadliest diseases, estimated to cause 9.9 million deaths in 2020. Conventional cancer treatments commonly involve mono‐chemotherapy or a combination of radiotherapy and mono‐chemotherapy. However, the negative side effects of these approaches have been extensively reported and have prompted the search for new therapeutic drugs. Over the past few years, numerous dietary agents, medicinal plants, and their phytochemicals gained considerable therapeutic importance because of their anticancer, antiviral, anti‐inflammatory, and antioxidant activities. Recent years have shown that essential oils possess therapeutic effects against numerous cancers. They are primarily used due to their lesser side effects than standard chemotherapeutic drugs. Carvacrol (CRV) is a phenolic monoterpenoid found in essential oils of oregano, thyme, pepperwort, wild bergamot, and other plants. Numerous anticancer reports of CRV substantiated that the main mechanistic action of CRV involves reduction in the viability of cancer cells and induction of apoptosis via both intrinsic and extrinsic pathways. CRV also obstructs the migration and invasion of cells leading to the suppressed proliferation rate. Furthermore, CRV mediates augmented ROS generation resulting in DNA damage and also halts the progression of cell cycle. Treatment of CRV modulates the expression of apoptotic proteins (Bax, Bad) and molecular targets of various signaling pathways (PI3K/AKT/mTOR, MAPKs, and Notch) in multiple solid carcinomas. Hence, this review aimed to acquire and disseminate the knowledge of chemopreventive and anticancer effects of CRV and the mechanisms of action already described for the compound against numerous cancers, including solid carcinomas, to guide future research. Practical applications Development and formulation of phytocompound based anticancer drug agents to counteract the aftereffects of chemotherapeutic drugs is a propitious approach. CRV is a monoterpenoid consisting of a phenolic group obtained from the essential oils of oregano and thyme. These plants are being used as food flavoring spice and as fragrance ingredient in various cosmetic formulations. For the use of CRV as an efficient chemopreventive agent, different therapeutic interactions of CRV along with its targeted pathways and molecules, involved in the regulation of onset and progression of various types of solid carcinomas, need to be studied and explored thoroughly.

Anti-Inflammatory and Antioxidant Effects of Carvacrol on N-Methyl-N′-Nitro-N-Nitrosoguanidine (MNNG) Induced Gastric Carcinogenesis in Wistar Rats

“…Plant species of the Lamiaceae family are rich in phenolic compounds and are mainly used as dried products for culinary purposes and herbal medicine [ 55 ]. Carvacrol, as a major component of these plants, has gained great scientific interest [ 15 ]. However, the application of carvacrol may be limited due to its volatile nature, low water solubility, and poor bioavailability due to its excretion after 24 h in urine.…”

“…In a study conducted in rats, the effect of Thymus vulgaris on antioxidant enzyme activity in various organs was investigated and it was found that T. vulgaris consumed as a dietary component reduced the age-related decline in superoxide dismutase enzymes in the liver and heart of aged rats [ 13 ]. One active substance representing a significant part of the essential oils of Lamiaceae plants is the monoterpenoid phenol carvacrol (5-isoropyl-2-methylphenol) [ 14 , 15 ]. Previously, it has been reported that carvacrol metabolizes fast due to its ring hydroxylation chemical structure, and is excreted after 24 h in the urine of rats [ 16 ].…”

“…Phenolic antioxidants such as carvacrol can lose their antioxidant properties at higher concentrations and gain a pro-oxidant status that induces oxidative stress by generating ROS and apoptosis [ 15 ]. In addition to having an anti-oxidant effect, carvacrol is one of the most potent anti-inflammatory compounds characterized through a decrease in the TNF-α level, a suppression of cyclooxygenase-2 expression, and an inhibition of nitric oxide production [ 20 ].…”

A Focused Insight into Thyme: Biological, Chemical, and Therapeutic Properties of an Indigenous Mediterranean Herb

“…The chemotherapeutic antitumor drugs used traditionally for the treatment of cancer patients showed high cytotoxicity to the tumor as well as normal tissues [ 55 , 58 ]. Therefore, searches for new therapeutic options, including medicinal plants and their phytochemicals, has been promoted due to their lower risk of side effects compared to standard chemotherapeutic drugs [ 59 ]. Numerous studies have demonstrated the beneficial effects of different medicinal plant extracts and their ability to exert damaging effects on cancer cells through various molecular mechanisms, including intrinsic or extrinsic caspase-dependent apoptosis, autophagy, and necroptosis [ 60 , 61 , 62 ].…”

“…Carvacrol and thymol exerted anticancer effects in various types of cell lines mimicking human cancers and they demonstrated their potential as chemopreventive or anticancer agents in different types of cancers [ 55 , 65 , 66 ]. Their major mechanisms of anticancer actions include induction of apoptosis, inhibition of cell growth (antiproliferative effect), augmentation of ROS generation, depolarization of mitochondrial membrane, activation of Bax proapoptotic mitochondrial proteins, inhibition of angiogenesis, interaction with caspase or poly-ADP ribose polymerase, and diminution of tumorigenesis by modulating the activity of carcinogen metabolizing enzymes [ 59 , 65 , 67 ].…”