Anti-Breast cancer effect of Rhus Coriaria extract

Plants have been shown to be an excellent source of new drugs, including anticancer agents. Rhus coriaria, commonly known as sumac, a plant that is known to possess different therapeutic values including anti-oxidant and anti-microbial activities. Here, we investigated the anti-cancer effect of R. coriaria on triple negative MDA-MB-231 cell line. We demonstrated that Rhus coriaria ethanolic extract (RCE) inhibits the proliferation of MDA-MB-231 cell line in a time- and concentration dependent manner. RCE induced senescence and cell cycle arrest at G1 phase. Moreover, no proliferative recovery was detected after RCE removal. Annexin V staining and PARP cleavage analysis revealed a minimal induction of apoptosis in MDA-MB-231 cells. Autophagy vacuoles were detected along with autophagy markers. Interestingly, blocking autophagy by 3-methyladenine (3-MA) or chloroquine (CQ) reduced RCE-induced cell death and senescence. Finally, RCE induced DNA damage, an event that was found to precede autophagy. Hence, altogether, these findings make Rhus coriaria a promising alternative candidate against breast cancer

Rhus coriaria suppresses angiogenesis, metastasis and tumor growth of breast cancer through inhibition of STAT3, NFκB and nitric oxide pathways

Recently, we reported that Rhus coriaria exhibits anticancer activities by promoting cell cycle arrest and autophagic cell death of the metastatic triple negative MDA-MB-231 breast cancer cells. Here, we investigated the effect of Rhus coriaria on the migration, invasion, metastasis and tumor growth of TNBC cells. Our current study revealed that non-cytotoxic concentrations of Rhus coriaria significantly inhibited migration and invasion, blocked adhesion to fibronectin and downregulated MMP-9 and prostaglandin E2 (PgE2). Not only did Rhus coriaria decrease their adhesion to HUVECs and to lung microvascular endothelial (HMVEC-L) cells, but it also inhibited the transendothelial migration of MDA-MB-231 cells through TNF-α-activated HUVECs. Furthermore, we found that Rhus coriaria inhibited angiogenesis, reduced VEGF production in both MDA-MB-231 and HUVECs and downregulated the inflammatory cytokines TNF-α, IL-6 and IL-8. The underlying mechanism for Rhus coriaria effects appears to be through inhibiting NFκB, STAT3 and nitric oxide (NO) pathways. Most importantly, by using chick embryo tumor growth assay, we showed that Rhus coriaria suppressed tumor growth and metastasis in vivo. The results described in the present study identify Rhus coriaria as a promising chemopreventive and therapeutic candidate that modulate triple negative breast cancer growth and metastasis.UAEU Program for Advanced Research (Grant 31S111-UPAR), the Zayed Center for Health Sciences (ZCHS) research grant (grant 31R021) and the Terry Fox Foundation Grant (2013) to Rabah Iratni

Rhus coriaria induces senescence and autophagic cell death in breast cancer cells through a mechanism involving p38 and ERK1/2 activation

Here, we investigated the anticancer effect of Rhus coriaria on three breast cancer cell lines. We demonstrated that Rhus coriaria ethanolic extract (RCE) inhibits the proliferation of these cell lines in a time- and concentration-dependent manner. RCE induced senescence and cell cycle arrest at G1 phase. These changes were concomitant with upregulation of p21, downregulation of cyclin D1, p27, PCNA, c-myc, phospho-RB and expression of senescence-associated β-galactosidase activity. No proliferative recovery was detected after RCE removal. Annexin V staining and PARP cleavage analysis revealed a minimal induction of apoptosis in MDA-MB-231 cells. Electron microscopy revealed the presence of autophagic vacuoles in RCE-treated cells. Interestingly, blocking autophagy by 3-methyladenine (3-MA) or chloroquine (CQ) reduced RCE-induced cell death and senescence. RCE was also found to activate p38 and ERK1/2 signaling pathways which coincided with induction of autophagy. Furthermore, we found that while both autophagy inhibitors abolished p38 phosphorylation, only CQ led to significant decrease in pERK1/2. Finally, RCE induced DNA damage and reduced mutant p53, two events that preceded autophagy. Our findings provide strong evidence that R. coriaria possesses strong anti-breast cancer activity through induction of senescence and autophagic cell death, making it a promising alternative or adjunct therapeutic candidate against breast cancer.UAEU Program for Advanced Research (Grant 31S111-UPAR) and by the Zayed Center for Health Sciences (ZCHS) research grant (grant 31R021) and College of Science Individual Research Grant (grant 31S123) to Rabah Iratni

DECIPHERING THE MOLECULAR MECHANISM THROUGH WHICH RHUS CORIARIA EXERTS ITS ANTI-CANCER ACTIVITY

Cancer remains a major health problem around the globe. Among various types of treatments, plants have been shown to have great capacity in cancer treatment, one of which is Rhus coriaria. Commonly known as sumac, Rhus coriaria is a culinary herb that is known to possess different therapeutic values including anti-oxidant and anti-microbial activities. In this Ph.D. project, we tested the effect of Rhus coriaria extract (RCE) on the migration, invasion, and metastasis of MDA-MB-231 human breast cancer cells. We showed that non-cytotoxic concentrations of RCE inhibited migration and invasion, blocked adhesion to fibronectin, and downregulated MMP-9. Additionally, we found that RCE reduced VEGF production and downregulated the inflammatory cytokines TNF-α and IL-6. The suggested mechanism for the effect of RCE appears to be through inhibiting NFκB and STAT3 pathways. Moreover, we extended our study and investigated the anti-cancer effect of RCE on HT-29 and Caco-2 human colorectal cancer cells. We found that RCE inhibited the viability and colony growth of colon cancer cells. RCE also induced Beclin-1-independent autophagy and caspase-7- dependent apoptosis. The suggested mechanism through which RCE exerts its effect is by inactivating AKT/mTOR pathway and downregulating Beclin-1, p53, and procaspase- 3 through targeting them to proteasome-dependent degradation. Proteasome inhibition restored these proteins to a level comparable to control cells and reduced RCE-induced cell death and blocked the activation of autophagy and apoptosis. Proteasomal degradation of mTOR was concomitant with an overall increase in proteins ubiquitination which targets the proteins for degradation by the proteasome. In conclusion, these preliminary results make Rhus coriaria a promising therapeutic candidate against both breast and colorectal cancer

Pharmacological and Antioxidant Activities of <i>Rhus coriaria</i> L. (Sumac)

Rhus coriaria L. (Anacardiaceae), commonly known as sumac, is a commonly used spice, condiment, and flavoring agent, especially in the Mediterranean region. Owing to its bountiful beneficial values, sumac has been used in traditional medicine for the management and treatment of many ailments including hemorrhoids, wound healing, diarrhea, ulcer, and eye inflammation. This plant is rich in various classes of phytochemicals including flavonoids, tannins, polyphenolic compounds, organic acids, and many others. By virtue of its bioactive, Rhus coriaria possesses powerful antioxidant capacities that have ameliorative and therapeutic benefits for many common diseases including cardiovascular disease, diabetes, and cancer. This review describes the phytochemical properties of R. coriaria and then focuses on the potent antioxidant capacities of sumac. We then dissect the cellular and molecular mechanisms of sumac’s action in modulating many pathophysiological instigators. We show how accumulating evidence supports the antibacterial, antinociceptive, antidiabetic, cardioprotective, neuroprotective, and anticancer effects of this plant, especially that toxicity studies show that sumac is very safe to consume by humans and has little toxicity. Taken together, the findings we summarize here support the utilization of this plant as an attractive target for drug discovery

Challenges and Recent Advances in Enzyme-Mediated Wastewater Remediation—A Review

Different classes of artificial pollutants, collectively called emerging pollutants, are detected in various water bodies, including lakes, rivers, and seas. Multiple studies have shown the devastating effects these emerging pollutants can have on human and aquatic life. The main reason for these emerging pollutants in the aquatic environment is their incomplete removal in the existing wastewater treatment plants (WWTPs). Several additional treatments that could potentially supplement existing WWTPs to eliminate these pollutants include a range of physicochemical and biological methods. The use of enzymes, specifically, oxidoreductases, are increasingly being studied for their ability to degrade different classes of organic compounds. These enzymes have been immobilized on different supports to promote their adoption as a cost-effective and recyclable remediation approach. Unfortunately, some of these techniques have shown a negative effect on the enzyme, including denaturation and loss of catalytic activity. This review focuses on the major challenges facing researchers working on the immobilization of peroxidases and the recent progress that has been made in this area. It focuses on four major areas: (1) stability of enzymes upon immobilization, enzyme engineering, and evolution; (2) recyclability and reusability, including immobilization on membranes and solid supports; (3) cost associated with enzyme-based remediation; and (4) scaling-up and bioreactors

Enzyme-immobilized hierarchically porous covalent organic framework biocomposite for catalytic degradation of broad-range emerging pollutants in water

Efficient enzyme immobilization is crucial for the successful commercialization of large-scale enzymatic water treatment. However, issues such as lack of high enzyme loading coupled with enzyme leaching present challenges for the widespread adoption of immobilized enzyme systems. The present study describes the development and bioremediation application of an enzyme biocomposite employing a cationic macrocycle-based covalent organic framework (COF) with hierarchical porosity for the immobilization of horseradish peroxidase (HRP). The intrinsic hierarchical porous features of the azacalix[4]arene-based COF (ACA-COF) allowed for a maximum HRP loading capacity of 0.76 mg/mg COF with low enzyme leaching ( 99 % degradation of seven diverse types of emerging pollutants (2-mercaptobenzothiazole, paracetamol, caffeic acid, methylparaben, furosemide, sulfamethoxazole, and salicylic acid)in under an hour. The described enzyme-COF system offers promise for efficient wastewater bioremediation applications