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 Interestingly, a literature survey combined with our unpublished data suggests that "peroxidases" are a very heterogeneous and diverse family of enzymes and have different pH profiles, temperature optima, thermal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.

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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.

We recently reported that carnosol induces ROS-dependent autophagy and apoptosis in breast cancer cells. We also reported that carnosol inhibits breast cancer cell migration, invasion, and in ovo tumor growth, as well as targets STAT3, PCAF, and p300 to proteasome degradation. Here, we investigated the molecular mechanisms underlying its anti-malignant activity in breast cancer. We report that carnosol induces a ROS-dependent type I and type II programmed cell death (PCD-I or PCD-II, respectively), which occurred independently of each other. Indeed, chemical inhibition of autophagy had no effect on the induction of apoptosis, evident by the absence of cleaved PARP. Electron microscopy revealed that carnosol-treated cells exhibited enlarged endoplasmic reticulum, characteristic of ER stress. Markers of the three unfolded protein response pathways (PERK, IRE-1 α, and ATF6), namely ATF4, CHOP, phospho-IRE-1α, XBP1S, and cleaved ATF6 were upregulated in a ROS-dependent manner. In addition, carnosol induced a ROS-dependent activation of p38MAPK, increased the overall level of protein polyubiquitination, and targeted mTOR protein to proteasome degradation. Interestingly, inhibition of p38MAPK, by SB202190 and 203580, reduced cell death, selectively blocked the induction of IRE-1α and ATF6 UPR sensors and inhibited autophagy. In addition, inhibition of p38 reduced the carnosol-induced polyubiquitination and rescued mTOR, PCAF, and STAT3 from proteasomal degradation. Importantly, activation of PERK sensors and induction of apoptosis occurred independently of p38 activation. Taken together, our results suggest that ROS-dependent induced-ER stress contributes to carnosol-induced apoptotic and autophagic cell death in breast cancer cells, and further confirm that carnosol is a promising agent for breast cancer therapy.