In vitro and in vivo antitumor potential of carvacrol nanoemulsion against human lung adenocarcinoma A549 cells via mitochondrial mediated apoptosis

Abstract

Carvacrol is present abundantly in the essential oils of many medicinal plants and well known for its numerous biological activities. Since partial solubility in water and physicochemical instability limits its industrial uses, the present study was performed to prepare a carvacrol nanoemulsion (CANE) using an ultrasonication technique and further evaluation of its anticancer potential against human lung adenocarcinoma A549 cells. The nanoemulsion formulation was optimized by varying carvacrol and polysorbate 80 ratios and characterized by dynamic light scattering (DLS), which revealed a negative surface charge with a mean droplet size between 105.5 ± 3.4 to 169.8 ± 4.9 nm. The CANE induced reactive oxygen species (ROS) production in A549 cells, leading to activation of key regulators of apoptosis such as p-JNK, Bax and Bcl2 as well as release of cytochrome C, and activation of the caspase cascade. Suppression of mitochondrial ROS using Mito-TEMPO reversed the apoptotic potential of CANE signifying involvement of mitochondrial ROS in cell death. Beside, CANE displayed a strong antitumor potential in vivo using an athymic nude mice model. The results strongly support that CANE induced apoptosis in A549 cells by induction of ROS and could be a promising candidate for lung cancer therapy.

Carvacrol nanoemulsion evokes cell cycle arrest, apoptosis induction and autophagy inhibition in doxorubicin resistant-A549 cell line

“…In the quest to evaluate the possible mechanism by which CANE encountered the A549 DR cells, we evaluated its cytotoxic properties by MTT, LDH, clonogenicity and soft agar assay. Results showed a potential cytotoxic effect of CANE, which is in accordance with the published reports suggesting the anticancer role of carvacrol [10,24,39]. To the best of our knowledge, the present study is the first report showing the anticancer potential of CANE against drug resistant cancer cells (A549 DR ).…”

“…Various plants and their components have been utilized worldwide due to their health beneficiary effect. Carvacrol a monoterpenoid is one of the imperative segments of thyme and oregano plants [8][9][10], has been reported for anti-proliferative property against neuroblastoma, colon and lung carcinoma cell lines [10,[22][23][24][25][26]. However, its application often suffers owing to its physicochemical instability [26,27].…”

“…Therefore, it is important to enhance the self-life of these bioactive compounds by using different oil base, surfactants or linker [7]. Here, we used carvacrol, a monoterpenoid phenolic compound found in various aromatic plants such as Origanum vulgare, Origanum dictammus, Origanum majorana, Thymbra capitate, Satureja hortensis, Thymus vulgaris and Thymus zygis, Thymus serpyllum, and Satureja montana which possess many biological activities such as antibacterial, antioxidant, anti-viral and anticancer [8][9][10]. Carvacrol partial solubility in the water and instability towards light, pressure and heat are the major hurdles of its commercial application.…”

An Overview of Micro- and Nanoemulsions as Vehicles for Essential Oils: Formulation, Preparation and Stability

“…At the moment, the most commonly used are: sucrose esters, sorbitan fatty acid esters, glycerol fatty acid esters (polyglycerols), polyoxyethylene sorbitan fatty acid esters (polysorbates) and polyoxyethylene ether surfactants [58]. The two most used surfactants for the formulation of EOs-based colloidal systems are the polysorbates Tween 80 and Tween 20, since they have been demonstrated to give stable formulations without the need of a co-surfactant ( Figure 3) [59][60][61][62][63][64]. This is an advantageous aspect both from the formulation and toxicological point of view.…”

Choice of nanocarrier for pulmonary delivery of cancer therapeutics

“…One of the main applications of nanoemulsion is drug delivery and cancer therapy. Oil-in-water nanoemulsion has been adopted as the drug vehicle of choice in pulmonary delivery [11,12]. The safety of excipients/surfactants is the primary consideration in the development of a pulmonary nanoemulsion [13].…”