Abstract
Oliveria decumbens is an Iranian endemic plant used extensively in traditional medicine. Recently, some studies have been performed on biological effects of Oliveria essential oil (OEO). However, to our knowledge, the anticancer activity of OEO has not been reported. Based on our GC/MS analysis, the basic ingredients of OEO are thymol, carvacrol, p-cymene and γ-terpinene. Therefore, we used OEO and its main component, thymol, to explore their effects on cell growth inhibition and anticancer activity. Despite having a limited effect on L929 normal cells, OEO/thymol induced cytotoxicity in MDA-MB231 breast cancer monolayers (2D) and to a lesser extent in MDA-MB231 spheroids (3D). Flow cytometry, caspase-3 activity assay in treated monolayers/spheroids and also fluorescence staining and DNA fragmentation in treated monolayers demonstrated apoptotic death mode. Indeed, OEO/thymol increased the Reactive Oxygen Species (ROS) level leading to mitochondrial membrane potential (MMP, ΔΨm) loss, caspase-3 activation and DNA damage caused S-phase cell cycle arrest. Furthermore, immunoblotting studies revealed the activation of intrinsic and maybe extrinsic apoptosis pathways by OEO/thymol. Additionally, in-vitro experiments, indicated that OEO/thymol interacts with DNA via minor grooves confirmed by docking method. Altogether, our reports underlined the potential of OEO to be considered as a new candidate for cancer therapy.
Highlights
Essential Oils (EOs), described as ‘the soul of plants’ are volatile complexes found in the aromatic plants and are used in pharmaceutical, and food industries for their anti-inflammatory, anti-microbial and anti-oxidant properties[9,10,11]
Our overall outcomes indicated that the Oliveria essential oil (OEO)/thymol has significant anti-proliferative effects by inducing apoptosis in MDA-MB231 cells in 2D and 3D cultures, 3D spheroids exhibited more resistance to the OEO/ thymol
The present study provided a novel insight into the mechanism of action of OEO/thymol-induced apoptosis in cancer cells
Summary
Essential Oils (EOs), described as ‘the soul of plants’ are volatile complexes found in the aromatic plants and are used in pharmaceutical, and food industries for their anti-inflammatory, anti-microbial and anti-oxidant properties[9,10,11]. Our data showed that 24 h treatment with carvacrol decreases the viability of MDA-MB231 and MCF-7 monolayers in a concentration-dependent manner, with IC50 of 53 and 46.5 μg/ml respectively while the IC50 of p-cymene was approximately estimated to be 295.2 and 261 μg/ml in MDA-MB231 and MCF-7 cells (Fig. 3B,C). According to these results, carvacrol has the same cytotoxic effect, or even better, than thymol on the breast cancer cells while p-cymene inhibits the growth of these cancer cells in higher IC50 and p-cymene has no significant effects on these cells
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