Water contamination by various recalcitrant organic aromatic compounds is an emerging environmental issue that is increasingly attracting the attention of environmental scientists. A great majority of these recalcitrant pollutants are industrial wastes, textile dyes, pharmaceuticals, hormones, and personal care products that are discharged into wastewater. Not surprisingly, various chemical, physical, and biological strategies have been proposed and developed to remove and/or degrade these pollutants from contaminated water bodies. Biological approaches, specifically using oxidoreductase enzymes (such as peroxidases and laccases) for pollutant degradation are a relatively new and a promising research area that has potential advantages over other methods due to their higher efficiency and the ease of handling. This review focuses on the application of different classes of oxidoreductase enzymes to degrade various classes of organic pollutants. In addition to classifying these enzymes based on structural differences, the major factors that can affect their remediation ability, such as the class of peroxidases employed, pH, molecular structure of the pollutant, temperature, and the presence of redox mediators are also examined and discussed. Interestingly, a literature survey combined with our unpublished data suggests that "peroxidases" are a very heterogeneous and diverse family of enzymes and have different pH profiles, temperature optima, thermal stabilities, requirements for redox mediators, and substrate specificities as well as varying detoxification abilities. Additionally, remediation of real-life polluted samples by oxidoreductases is also highlighted as well as a critical look at current challenges and future perspectives.

Colorectal cancer (CRC) is the third most common type of cancer in terms of incidence and mortality worldwide. Here we have investigated the anti-colon cancer potential of Origanum majorana essential oil (OMEO) and its underlying mechanisms of action. We showed that OMEO significantly inhibited the cellular viability and colony growth of human HT-29 colorectal cancer cells. OMEO induced protective autophagy, associated with downregulation of the mTOR/p70S6K pathway, and activated caspase-8 and caspase-9-dependent apoptosis. Blockade of autophagy with 3-methyladenine (3-MA) and chloroquine (CQ), two autophagy inhibitors, potentiated the OMEO-induced apoptotic cell death. Inversely, inhibition of apoptosis with the pan-caspase inhibitor, Z-VAD-FMK, significantly reduced cell death, suggesting that apoptosis represents the main mechanism of OMEO-induced cell death. Mechanistically, we found that OMEO induces protective autophagy and apoptotic cells death via the activation of the p38 MAPK signaling pathway. Pharmacological inhibition of p38 MAPK by the p38 inhibitors SB 202190 and SB 203580 not only significantly decreased apoptotic cell death, but also reduced the autophagy level in OMEO treated HT-29 cells. Strikingly, we found that OMEO also induces p38 MAPK-mediated caspase-dependent cleavage of p70S6K, a protein reported to be overexpressed in colon cancer and associated with drug resistance. Our findings suggest that OMEO inhibits colon cancer through p38 MAPK-mediated protective autophagy and apoptosis associated with caspase-dependent cleavage of p70S6K. To the best of our knowledge, this study is the first to report on the implications of the p38 MAPK signaling pathway in targeting p70S6K to caspase cleavage.

Colorectal cancer is considered as the third leading cause of cancer death. In the present study, we investigated the potential anticancer effect and the molecular mechanism of Origanum majorana ethanolic extract (OME) against human colorectal cancer cells. We showed that OME exhibited strong anti-proliferative activity in a concentration- and time-dependent manner against two human colorectal cancer cell lines (HT-29 and Caco-2). OME inhibited cell viability, colony growth and induced mitotic arrest of HT-29 cells. Also, OME induced DNA damage, triggered abortive autophagy and activated a caspase 3 and 7-dependent extrinsic apoptotic pathway, most likely through activation of the TNFα pathway. Time-course analysis revealed that DNA damage occurred concomitantly with abortive autophagy after 4 h post-OME treatment while apoptosis was activated only 24 h later. Blockade of autophagy initiation, by 3-methyladenine, partially rescued OME-induced cell death. Cell viability arose from 37% in control group to 67% in group pre-treated with 3-MA before addition of OME. Inhibition of apoptosis, however, had a minimal effect on cell viability; it rose from 37% in control group to 43% in group pre-treated with Z-VAD-FMK. We also found that OME downregulated survivin in HT-29 cells. Our findings provide a strong evidence that O. majorana extract possesses strong anti-colon cancer potential, at least, through induction of autophagy and apoptosis. These finding provide the basis for therapeutic potential of O. majorana in the treatment of colon cancer.

The coronavirus disease-19 (COVID-19) pandemic is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). At the molecular and cellular levels, the SARS-CoV-2 uses its envelope glycoprotein, the spike S protein, to infect the target cells in the lungs via binding with their transmembrane receptor, the angiotensin-converting enzyme 2 (ACE2). Here, we wanted to investigate if other molecular targets and pathways may be used by SARS-CoV-2. We investigated the possibility of the spike 1 S protein and its receptor-binding domain (RBD) to target the epidermal growth factor receptor (EGFR) and its downstream signaling pathway in vitro using the lung cancer cell line (A549 cells). Protein expression and phosphorylation were examined upon cell treatment with the recombinant full spike 1 S protein or RBD. We demonstrate for the first time the activation of EGFR by the Spike 1 protein associated with the phosphorylation of the canonical Extracellular signal-regulated kinase1/2 (ERK1/2) and AKT kinases and an increase in survivin expression controlling the survival pathway. Our study suggests the putative implication of EGFR and its related signaling pathways in SARS-CoV-2 infectivity and COVID-19 pathology. This may open new perspectives in the treatment of COVID-19 patients by targeting EGFR.

Enzymatic degradation of organic pollutants is a new and promising remediation approach. Peroxidases are one of the most commonly used classes of enzymes to degrade organic pollutants. However, it is generally assumed that all peroxidases behave similarly and produce similar degradation products. In this study, we conducted detailed studies of the degradation of a model aromatic pollutant, Sulforhodamine B dye (SRB dye), using two peroxidases—soybean peroxidase (SBP) and chloroperoxidase (CPO). Our results show that these two related enzymes had different optimum conditions (pH, temperature, H₂O₂ concentration, etc.) for efficiently degrading SRB dye. High-performance liquid chromatography and liquid chromatography –mass spectrometry analyses confirmed that both SBP and CPO transformed the SRB dye into low molecular weight intermediates. While most of the intermediates produced by the two enzymes were the same, the CPO treatment produced at least one different intermediate. Furthermore, toxicological evaluation using lettuce (Lactuca sativa) seeds demonstrated that the SBP-based treatment was able to eliminate the phytotoxicity of SRB dye, but the CPO-based treatment did not. Our results show, for the first time, that while both of these related enzymes can be used to efficiently degrade organic pollutants, they have different optimum reaction conditions and may not be equally efficient in detoxification of organic pollutants.