Ziziphus nummularia attenuates the malignant phenotype of human pancreatic cancer cells: Role of ros

Pancreatic cancer (PC) is the fourth leading cause of all cancer-related deaths. Despite major improvements in treating PC, low survival rate remains a major challenge, indicating the need for alternative approaches, including herbal medicine. Among medicinal plants is Ziziphus nummu-laria (family Rhamnaceae), which is a thorny shrub rich in bioactive molecules. Leaves of Ziziphus nummularia have been used to treat many pathological conditions, including cancer. However, their effects on human PC are still unknown. Here, we show that the treatment of human pancreatic ductal adenocarcinoma cells (Capan-2) with Ziziphus nummularia ethanolic extract (ZNE) (100–300 µg/mL) attenuated cell proliferation in a time-and concentration-dependent manner. Pretreatment with N-acetylcysteine, an ROS scavenger, attenuated the anti-proliferative effect of ZNE. In addition, ZNE significantly decreased the migratory and invasive capacity of Capan-2 with a concomitant downregulation of integrin α2 and increased cell–cell aggregation. In addition, ZNE inhibited in ovo angiogenesis as well as reduced VEGF and nitric oxide levels. Furthermore, ZNE downregulated the ERK1/2 and NF-κB signaling pathways, which are known to drive tumorigenic and metastatic events. Taken together, our results suggest that ZNE can attenuate the malignant phenotype of Capan-2 by inhibiting hallmarks of PC. Our data also provide evidence for the potential anticancer effect of Ziziphus nummularia, which may represent a new resource of novel anticancer compounds, especially ones that can be utilized for the management of PC

Origanum syriacum L. Attenuates the Malignant Phenotype of MDA-MB231 Breast Cancer Cells

Breast cancer is the leading cause of cancer-related deaths among women. Among breast cancer types, triple negative breast cancer (TNBC) is the most aggressive, and is resistant to hormonal and chemotherapeutic treatments. As such, alternative approaches that may provide some benefit in fighting this debilitating pathology are critically needed; hence the utilization of herbal medicine. Origanum syriacum L., one of the most regularly consumed plants in the Mediterranean region, exhibits antiproliferative effect on several cancer cell lines. However, whether this herb modulates the malignant phenotype of TNBC remains poorly investigated. Here, we show that in MDA-MB-231, a TNBC cell line, Origanum syriacum L. aqueous extract (OSE) inhibited cellular viability, induced autophagy determined by the accumulation of lipidized LC3 II, and triggered apoptosis. We also show that OSE significantly promoted homotypic cell-cell adhesion while it decreased cellular migration, adhesion to fibronectin, and invasion of MDA-MB-231 cells. This was supported by decreased activity of focal adhesion kinase (FAK), reduced α2 integrin expression, and downregulation of secreted PgE2, MMP2 and MMP-9, in OSE-treated cells. Finally, we also show that OSE significantly inhibited angiogenesis and downregulated the level of nitric oxide (NO) production. Our findings demonstrate the ability of OSE to attenuate the malignant phenotype of the MDA-MB-231 cells, thus presenting Origanum syriacum L. as a promising potential source for therapeutic compounds for TNBC

Ethanolic Extract of Origanum syriacum L. Leaves Exhibits Potent Anti-Breast Cancer Potential and Robust Antioxidant Properties

International audienceBackground: Breast cancer (BC) is the second most common cancer overall. In women, BC is the most prevalent cancer and the leading cause of cancer-related mortality. Triple negative BC (TNBC) is the most aggressive BC being resistant to hormonal and targeted therapies.Hypothesis/Purpose: The medicinal plant Origanum syriacum is a shrubby plant rich in bioactive compounds and widely used in traditional medicine to treat various diseases. However, its therapeutic potential against BC remains poorly investigated. In the present study, we identified the bioactive compounds of the ethanolic extract of O. syriacum (OSEE) and investigated its anticancer effects and possible underlying mechanisms of action against the aggressive and highly metastatic human TNBC cell line MDA-MB-231.Methods: Column chromatography and LC-MS were used to identify the phytochemical constituents of OSEE, MTT, trans-well migration, and scratch assays were used to assess cell viability, invasion, or migration, respectively. Antioxidant potential was evaluated in vitro using the DPPH radical scavenging assay and ROS levels were assessed in cells in culture using DHE staining. Aggregation assays were used to determine cell-cell adhesion. Flow cytometry was used to analyze cell cycle progression. Protein levels of markers of apoptosis (BCL-2, pro-Capase3, p53), proliferation (p21, Ki67), cell migration, invasion, or adhesion (FAK, E-cadherin), angiogenesis (iNOS), and cell signaling (STAT3, p38) were determined by immunoblotting. Chorio-allontoic Membrane (CAM) assay evaluated in ovo angiogenesis.Results: We demonstrated that OSEE was rich in phytochemical constituents mainly carvacrol. We also found that the OSEE crude extract had potent radical scavenging activity in vitro and induced the generation of reactive oxygen species (ROS) in MDA-MB-231 cells, especially at higher OSEE concentrations. Non-cytotoxic concentrations of OSEE attenuated cell proliferation and induced G0/G1 cell cycle arrest, which was associated with phosphorylation of p38 MAPK, an increase in the levels of tumor suppressor protein p21, and a decrease of proliferation marker protein Ki67. Additionally, only higher concentrations of OSEE were able to attenuate inhibition of proliferation induced by the ROS scavenger N-acetyl cysteine (NAC), proposing that the anti-proliferative effects of OSEE can be ROS-dependent. OSEE stimulated apoptosis and its effector Caspase-3 in MDA-MB-231 cells, in correlation with activation of STAT3/p53 pathway. Furthermore, the extract reduced the migration and invasive properties of MDA-MB-231 cells through the deactivation of focal adhesion kinase (FAK). OSEE also reduced the production of inducible nitric oxide synthase (iNOS) and inhibited in ovo angiogenesis. Further studies have been carried out to assess the composition of various fractions from the OSEE crude extract, in an effort to identify the bioactive molecules. Interestingly, two fractions have shown a more potent activity against the proliferation of MDA-MB-231 cells when compared to the crude extract.Conclusion: Our findings reveal that OSEE is a rich source of phytochemicals and has robust anti-breast cancer properties that significantly attenuate the malignant phenotype of MDA-MB-231 cells, suggesting that Origanum syriacum may act as a rich source of potential TNBC therapeutics and poising Origanum syriacum to offer novel avenues for the design novel TNBC drugs

Origanum syriacum Phytochemistry and Pharmacological Properties: A Comprehensive Review

Herbal medicine has been gaining special interest as an alternative choice of treatment for several diseases, being generally accessible, cost-effective and safe, with fewer side-effects compared to chemically synthesized medicines. Over 25% of drugs worldwide are derived from plants, and surveys have shown that, when available, herbal medicine is the preferred choice of treatment. Origanum syriacum (Lamiaceae) is a widely used medicinal plant in the Middle East, both as a home and a folk remedy, and in the food and beverage industry. Origanum syriacum contains numerous phytochemical compounds, including flavonoids, phenols, essential oils, and many others. Because of its bioactive compounds, O. syriacum possesses antioxidant, antimicrobial, and antiparasitic capacities. In addition, it can be beneficial in the treatment of various diseases such as cancer, neurodegenerative disorders, and peptic ulcers. In this review, the chemical compositions of different types of extracts and essential oils from this herb will first be specified. Then, the pharmacological uses of these extracts and essential oils in various contexts and diseases will be discussed, putting emphasis on their efficacy and safety. Finally, the cellular and molecular mechanisms of O. syriacum phytochemicals in disease treatment will be described as a basis for further investigation into the plant's pharmacological role

On the usefulness of information hiding techniques for wireless sensor networks security

International audienceA wireless sensor network (WSN) typically consists of base stations and a large number of wireless sensors. The sensory data gathered from the whole network at a certain time snapshot can be visualized as an image. As a result, information hiding techniques can be applied to this “sensory data image”. Steganography refers to the technology of hiding data into digital media without drawing any suspicion, while steganalysis is the art of detecting the presence of steganography. This article provides a brief review of steganography and steganalysis applications for wireless sensor networks (WSNs). Then we show that the steganographic techniques are both related to sensed data authentication in wireless sensor networks, and when considering the attacker point of view, which has not yet been investigated in the literature. Our simulation results show that the sink level is unable to detect an attack carried out by the nsF5 algorithm on sensed data

Ziziphus nummularia: A Comprehensive Review of Its Phytochemical Constituents and Pharmacological Properties

Ziziphus nummularia, a small bush of the Rhamnaceae family, has been widely used in traditional folk medicine, is rich in bioactive molecules, and has many reported pharmacological and therapeutic properties. Objective: To gather the current knowledge related to the medicinal characteristics of Z. nummularia. Specifically, its phytochemical contents and pharmacological activities in the treatment of various diseases such as cancer, diabetes, and cardiovascular diseases, are discussed. Methods: Major scientific literature databases, including PubMed, Scopus, ScienceDirect, SciFinder, Chemical Abstracts, Medicinal and Aromatic Plants Abstracts, Henriette′s Herbal Homepage, Dr. Duke′s Phytochemical and Ethnobotanical Databases, were searched to retrieve articles related to the review subject. General web searches using Google and Google scholar were also utilized. The search period covered articles published between 1980 and the end of October 2021.The search used the keywords 'Ziziphus nummularia', AND ('phytochemical content', 'pharmacological properties, or activities, or effects, or roles', 'anti-inflammatory', 'anti-drought', 'anti-thermal', 'anthelmintic', 'antidiabetic',' anticancer', 'anticholinesterase', 'antimicrobial', 'sedative', 'antipyretic', 'analgesic', or 'gastrointestinal'). Results: This plant is rich in characteristic alkaloids, especially cyclopeptide alkaloids such as nummularine-M. Other phytochemicals, including flavonoids, saponins, glycosides, tannins, and phenolic compounds, are also present. These phytochemicals are responsible for the reported pharmacological properties of Z. nummularia, including anti-inflammatory, antioxidant, antimicrobial, anthelmintic, antidiabetic, anticancer, analgesic, and gastrointestinal activities. In addition, Z. nummularia has anti-drought and antithermal characteristics. Conclusion: Research into the phytochemical and pharmacological properties of Z. nummularia has demonstrated that this plant is a rich source of novel bioactive compounds. So far, Z. nummularia has shown a varied pharmacological profile (antioxidant, anticancer, anti-inflammatory, and cardioprotective), warranting further research to uncover the therapeutic potential of the bioactives of this plant. Taken together, Z. nummularia may represent a new potential target for the discovery of new drug leads

Comparing Emergent and Elective Colectomy Outcomes in Elderly Patients: A NSQIP Study

Introduction. With the increasing prevalence of colorectal cancer (CRC) worldwide, especially in the elderly, and the variability between physiological and chronological age and its impact on functional status, acute symptoms leading to emergent surgery due to colorectal malignancy may lead to increased morbidity and mortality. The aim of this study is to identify the outcome differences of elective vs. emergent open colectomy in patients above 80 years. Methods. The National Surgical Quality Improvement Program (NSQIP) database was reviewed from 2010 to 2014 for open colectomy based on CPT codes. Comparison between groups was done based on the clinical context at presentation as elective or emergent surgery. Data were analyzed using SAS. Results. Elective colectomies were performed in 8289 (70.8%) vs. emergent colectomies in 3409 (29.1%). Emergent colectomy patients had higher American Society of Anesthesiologists (ASA) preoperative classification III-IV, 1429 (42.0%) and 224 (6.6%), vs. 1238 (14.9%) and 21 (0.2%) in elective colectomy patients p<0.0001. Emergent colectomy patients had more comorbidities such as chronic obstructive pulmonary disorder (493 (14.5%) vs. 796 (9.6%)), congestive heart failure (206 (6.0%) vs. 310 (3.8%)), dialysis (106 (3.1%) vs. 56 (0.7%)), and acute renal failure (166 (4.9%) vs. 46 (0.6%)) p<0.0001, respectively. Postoperative morbidity and mortality were significantly higher in emergent colectomy (1651 (48.4%) and 872 (25.6%)) vs. elective colectomy (1859 (22.4%) and 567 (6.8%)) p<0.0001, respectively. Conclusion. Emergent open colectomy in elderly patients carries a higher risk of morbidity and mortality when compared to elective open colectomy with risk factors being higher ASA classification and more comorbidities

Study of the antioxidant and anti-pancreatic cancer activities of Anchusa strigosa aqueous extracts obtained by maceration and ultrasonic extraction techniques

International audiencePancreatic cancer is a highly aggressive malignancy and a leading cause of cancer-related deaths worldwide. Moreover, the incidence and mortality rates for pancreatic cancer are projected to keep increasing. A major challenge in the treatment of pancreatic cancer is the lack of effective screening approaches, which contributes to its poor prognosis, indicating the need for new treatment regimens and alternative therapies, such as herbal medicine. The medicinal plant A. strigosa , which is widely distributed in the Eastern Mediterranean region, is a short prickly plant from the Boraginaceae family that has been widely used in traditional medicine for treating various diseases. Nevertheless, its effect on human pancreatic cancer remains poorly investigated. In the present study, we screened the phytochemical content of Anchusa strigosa aqueous extracts obtained by maceration and ultrasound-assisted methods (ASM and ASU, respectively) and evaluated their antioxidant effects. We also investigated their anticancer effects and possible underlying mechanisms. The results show that both extracts were rich in bioactive molecules, with slight differences in their composition. Both extracts exhibited remarkable antioxidant potential and potent radical-scavenging activity in vitro . Additionally, non-cytotoxic concentrations of both extracts attenuated cell proliferation in a time- and concentration-dependent manner, which was associated with a decrease in the proliferation marker Ki67 and an induction of the intrinsic apoptotic pathway. Furthermore, the extracts increased the aggregation of pancreatic cancer cells and reduced their migratory potential, with a concomitant downregulation of integrin β1. Finally, we showed that the ASM extract caused a significant decrease in the levels of COX-2, an enzyme that has been linked to inflammation, carcinogenesis, tumor progression, and metastasis. Taken together, our findings provide evidence that A. strigosa extracts, particularly the extract obtained using the maceration method, have a potential anticancer effect and may represent a new resource for the design of novel drugs against pancreatic cancer

Ethanolic Extract of Origanum Syriacum L. Leaves Exhibits Potent Anti-Breast Cancer Potential and Robust Antioxidant Properties.

International audienceBackground: Breast cancer (BC) is the second most common cancer overall. In women, BC is the most prevalent cancer and the leading cause of cancer-related mortality. Triple-negative BC (TNBC) is the most aggressive BC, being resistant to hormonal and targeted therapies. HYPOTHESIS/PURPOSE: The medicinal plant Origanum syriacum L. is a shrubby plant rich in bioactive compounds and widely used in traditional medicine to treat various diseases. However, its therapeutic potential against BC remains poorly investigated. In the present study, we screened the phytochemical content of an ethanolic extract of O. syriacum (OSEE) and investigated its anticancer effects and possible underlying mechanisms of action against the aggressive and highly metastatic human TNBC cell line MDA-MB-231. METHODS: MTT, trans-well migration, and scratch assays were used to assess cell viability, invasion, or migration, respectively. Antioxidant potential was evaluated in vitro using the DPPH radical-scavenging assay and levels of reactive oxygen species (ROS) were assessed in cells in culture using DHE staining. Aggregation assays were used to determine cell-cell adhesion. Flow cytometry was used to analyze cell cycle progression. Protein levels of markers of apoptosis (BCL-2, pro-Caspase3, p53), proliferation (p21, Ki67), cell migration, invasion, or adhesion (FAK, E-cadherin), angiogenesis (iNOS), and cell signaling (STAT3, p38) were determined by immunoblotting. A chorioallantoic Membrane (CAM) assay evaluated in ovo angiogenesis. RESULTS: We demonstrated that OSEE had potent radical scavenging activity in vitro and induced the generation of ROS in MDA-MB-231 cells, especially at higher OSEE concentrations. Non-cytotoxic concentrations of OSEE attenuated cell proliferation and induced G(0)/G(1) cell cycle arrest, which was associated with phosphorylation of p38 MAPK, an increase in the levels of tumor suppressor protein p21, and a decrease of proliferation marker protein Ki67. Additionally, only higher concentrations of OSEE were able to attenuate inhibition of proliferation induced by the ROS scavenger N-acetyl cysteine (NAC), indicating that the anti-proliferative effects of OSEE could be ROS-dependent. OSEE stimulated apoptosis and its effector Caspase-3 in MDA-MB-231 cells, in correlation with activation of the STAT3/p53 pathway. Furthermore, the extract reduced the migration and invasive properties of MDA-MB-231 cells through the deactivation of focal adhesion kinase (FAK). OSEE also reduced the production of inducible nitric oxide synthase (iNOS) and inhibited in ovo angiogenesis. CONCLUSION: Our findings reveal that OSEE is a rich source of phytochemicals and has robust anti-breast cancer properties that significantly attenuate the malignant phenotype of MD-MB-231 cells, suggesting that O. syriacum may not only act as a rich source of potential TNBC therapeutics but may also provide new avenues for the design of novel TNBC drugs