Potential Anti-Tumorigenic Properties of Diverse Medicinal Plants against the Majority of Common Types of Cancer.

Globally, cancer is one of the primary causes of both morbidity and mortality. To prevent cancer from getting worse, more targeted and efficient treatment plans must be developed immediately. Recent research has demonstrated the benefits of natural products for several illnesses, and these products have played a significant role in the development of novel treatments whose bioactive components serve as both chemotherapeutic and chemo-preventive agents. Phytochemicals are naturally occurring molecules obtained from plants that have potential applications in both cancer therapy and the development of new medications. These phytochemicals function by regulating the molecular pathways connected to the onset and progression of cancer. Among the specific methods are immune system control, inducing cell cycle arrest and apoptosis, preventing proliferation, raising antioxidant status, and inactivating carcinogens. A thorough literature review was conducted using Google Scholar, PubMed, Scopus, Google Patent, Patent Scope, and US Patent to obtain the data. To provide an overview of the anticancer effects of several medicinal plants, including Annona muricata, Arctium lappa, Arum palaestinum, Cannabis sativa, Catharanthus roseus, Curcuma longa, Glycyrrhiza glabra, Hibiscus, Kalanchoe blossfeldiana, Moringa oleifera, Nerium oleander, Silybum marianum, Taraxacum officinale, Urtica dioica, Withania somnifera L., their availability, classification, active components, pharmacological activities, signaling mechanisms, and potential side effects against the most common cancer types were explored.

Cymbopogon winterianus (Java Citronella Plant): A Multi-Faceted Approach for Food Preservation, Insecticidal Effects, and Bread Application.

Certain plants like Rosemarinus officinalis, Lavandula angustifolia and Origanum vulgare have been used in the food industry for centuries. Cymbopogon winterianus (Java Citronella plant) is one of the most significant plants. The objective of this study is to screen for secondary metabolites by phytochemical screening, evaluate the antioxidant contents of extracts and investigate the use of the Java Citronella plant in food preservation and as an insecticide. Java Citronella powder was added to bread and evaluated for its moisture content, and a visual and sensory analysis was performed. Sitophilus granarius (L.) weevils were exposed to Java Citronella essential oil (JCEO). The phytochemical screening revealed that the extracts were abundant in secondary metabolites. The JCEO had a yield of 0.75%. The aqueous extract had a higher total phenolic content of 49.043 ± 0.217 mg GAE/g than the ethanolic extract, which was 24.478 ± 1.956 mg GAE/g. The aqueous extract had a total flavonoids content 27,725.25 ± 54.96 µg RE/g higher than the ethanolic extract, with 24,263 ± 74 µg RE/g. The ethanolic extract had stronger antioxidant activity, with anIC50 = 196.116 µg/mL higher than the aqueous extract at 420 µg/mL. The 2% Java Citronella powder in the bread was preferred by consumers, and had a shelf life of 6 days. JCEO killed all the weevils with a high dose of 10% after 48 h. The Java Citronella showed insecticidal and food preservative activity. The results should help in future research to enhance the applications of Java Citronella in various domains, from food technology to insecticides.

Fractionation and phytochemical composition of an ethanolic extract of Ziziphus nummularia leaves: antioxidant and anticancerous properties in human triple negative breast cancer cells.

Natural products have long been utilized in traditional medicine as remedies to improve health and treat illnesses, and have had a key role in modern drug discovery. Recently, there has been a revived interest in the search for bioactives from natural sources as alternative or complementary modalities to synthetic medicines; especially for cancer treatment, which incidence and mortality rates are on the rise worldwide. Ziziphus nummularia has been widely used in traditional medicine for the treatment of various diseases. Its traditional uses and numerous ethnopharmacological properties may be attributed to its richness in bioactive metabolites. However, its phytochemical composition or chemopreventive effects against the aggressive triple-negative breast cancer (TNBC) are still poorly explored. Here, phytochemical composition of an ethanolic extract of Z. nummularia leaves (ZNE) and its chromatographically isolated fractions was identified both qualitatively by spectrophotometric assays and analytically by HPLC-PDA-MS/MS. The anti-proliferative effects of ZNE were tested in several cancer cell lines, but we focused on its anti-TNBC effects since they were not explored yet. The anti-cancerous potential of ZNE and its fractions was tested in vitro in MDA-MB-231, a TNBC cell line. Results showed that ZNE and its Fraction 6 (F6) reduced the viability of MDA-MB-231 cells. F6 decreased MDA-MB-231 viability more than crude ZNE or its other fractions. ZNE and F6 are rich in phytochemicals and HPLC-PDA-MS/MS analysis identified several metabolites that were previously reported to have anti-cancerous effects. Both ZNE and F6 showed potent antioxidant capacity in the DPPH assay, but promoted reactive oxygen species (ROS) production in MDA-MB-231 cells; an effect which was blunted by the antioxidant N-acetyl cysteine (NAC). NAC also blunted ZNE- and F6-induced reduction in TNBC cell viability. We also demonstrated that ZNE and F6 induced an arrest of the cell cycle, and triggered apoptosis- and autophagy-mediated cell death. ZNE and F6 inhibited metastasis-related cellular processes by modifying cell migration, invasion, and adhesion. Taken together, our findings reveal that Z. nummularia is rich in phytochemicals that can attenuate the malignant phenotype of TNBC and may offer innovative avenues for the discovery of new drug leads for treatment of TNBC and other cancers.

A Novel Deleterious MYO15A Gene Mutation Causes Nonsyndromic Hearing Loss.

Introduction: Hearing loss (HL) is the most frequent sensory neurodeficiency, affecting a broad spectrum of individuals globally. Within this context, the role of genetic factors takes center stage, particularly in cases of hereditary HL. Case Report: Here, we present a nonsyndromic HL (NSHL) case report. The patient is a 21-year-old man with progressive HL. The whole-exome sequencing (WES) demonstrated a novel homozygous missense mutation, c.9908A>C; p.Lys3303Thr, in the proband's exon 61 of the MYO15A gene. Further analysis has revealed that the detected mutation is present in a heterozygous state in the parents. Conclusion: WES analysis in this study revealed a novel mutation in the MYO15A gene. Our data indicates that the MYO15A-p.Lys3303Thr mutation is the likely pathogenic variant associated with NSHL. Additionally, this finding enhances genetic counseling for individuals with NSHL patients, highlighting the value of the WES method in detecting rare genetic variants.

Ethnopharmacology and therapeutic potential of Anchusa strigosa: a comprehensive review.

Anchusa strigosa Banks and Sol. is a rough flowering plant of the Boraginaceae family native to Eastern Mediterranean region that is widely used in traditional herbal medicine, mainly for the treatment of wounds, abdominal pain, and arthritis, to name a few. This article aims to gather knowledge related to the medicinal properties of A. strigosa. Specifically, it summarizes its traditional uses and pharmacological activities in the treatment of various diseases. Moreover, its botanical, ecological, and phytochemical characteristics are also discussed. Research showed that this plant is rich in pyrrolizidine alkaloids, particularly in the leaves. Other bioactive metabolites identified in this plant include flavonoids, phenolic acids, triterpenes, organic acids, and volatile organic compounds. These phytochemicals are responsible for the reported pharmacological properties of A. strigosa, including antimicrobial, antioxidant, anticancer, anti-inflammatory, antiarthritic, gastric protective, antidiabetic, and pro-wound healing. This warrants further investigation into the molecular mechanism of action behind the observed effects to elucidate its therapeutic potential. Nevertheless, more research on this plant is needed to ensure its efficacy and safety.

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

Pancreatic 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 ß1. 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.

The Therapeutic Wound Healing Bioactivities of Various Medicinal Plants.

The skin serves as the body's first line of defense, guarding against mechanical, chemical, and thermal damage to the interior organs. It includes a highly developed immune response that serves as a barrier against pathogenic infections. Wound healing is a dynamic process underpinned by numerous cellular activities, including homeostasis, inflammation, proliferation, and remodeling, that require proper harmonious integration to effectively repair the damaged tissue. Following cutaneous damage, microorganisms can quickly enter the tissues beneath the skin, which can result in chronic wounds and fatal infections. Natural phytomedicines that possess considerable pharmacological properties have been widely and effectively employed forwound treatment and infection prevention. Since ancient times, phytotherapy has been able to efficiently treat cutaneous wounds, reduce the onset of infections, and minimize the usage of antibiotics that cause critical antibiotic resistance. There are a remarkable number of wound-healing botanicals that have been widely used in the Northern Hemisphere, including Achiella millefolium, Aloe vera, Althaea officinalis, Calendula officinalis, Matricaria chamomilla, Curcuma longa, Eucalyptus, Jojoba, plantain, pine, green tea, pomegranate, and Inula. This review addresses the most often used medicinal plants from the Northern Hemisphere that facilitate the treatment of wounds, and also suggests viable natural alternatives that can be used in the field of wound care.

Ethanolic extract of Origanum syriacum L. leaves exhibits potent anti-breast cancer potential and robust antioxidant properties.

Background: 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 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), 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.

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.

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 anti-thermal 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.

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.

Liposome-based nanocapsules for the controlled release of dietary curcumin: PDDA and silica nanoparticle-coated DMPC liposomes enhance the fluorescence efficiency and anticancer activity of curcumin.

Nanosystems with various compositions and biological properties are being extensively investigated for drug and gene delivery applications. Many nanotechnology methods use novel nanocarriers, such as liposomes, in therapeutically targeted drug delivery systems. However, liposome matrices suffer from several limitations, including drug leakage and instability. Therefore, the surface modification of liposomes by coating them or adding polymers has advanced their application in drug delivery. Hence, the prevention of drug release from the liposome bilayers was the main focus of this work. For this purpose, liposomes were synthesized according to a thin film hydration method by applying various surface modifications. Three different nanocapsules, N1, N2, and N3, were prepared using 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), poly(diallyldimethylammonium)chloride (PDAA) polymer, and silica nanoparticles. PDDA and silica nanoparticles were coated on the surface of liposomes using a layer-by-layer assembly method, completely encapsulating curcumin into the core of the liposome. Fluorescence spectroscopy, TGA, DLS, XRD, SEM, and zeta potential methods were used to characterize the prepared nanocapsules. Interestingly, the fluorescence of curcumin showed a blue shift and the fluorescence efficiency was extraordinarily enhanced ∼25-, ∼54-, and ∼62-fold in the N1, N2, and N3 nanocapsules, respectively. Similarly, encapsulation efficiency, drug loading, and the anticancer activity of dietary curcumin were investigated for the different types of DMPC nanocapsules. The drug efficiencies of the liposomes were established according to the release of curcumin from the liposomes. The results showed that the release of curcumin from the nanocapsules decreased as the number of layers at the surface of the liposomes increased. The release of curcumin follows the Higuchi model; thus, a slow rate of diffusion is observed when a number of layers is added. The better encapsulation and higher anti-cancer activity of curcumin were also observed when more layers were added, which is due to electrostatic interactions inhibiting curcumin from being released.

Y-chromosome variation in Basrah population.

Y-chromosome DNA profiles are promising tools in population genetics and forensic science. Analysis of Y-chromosome variety was performed on a total of 191 unrelated males throughout different regions in Basrah. The Y-chromosome variety was explored utilizing 17 markers system. For the uniparental system, the large majority of the haplogroups observed in the Basrah population are (R1b, E1b1b, G2a, and J1) considered to have begun in the Middle East and to have later spread all over Western Eurasia. 30% of the Y-chromosomes, in all likelihood, represent landings from inaccessible distant geographic regions. The level of haplotype diversity and its implication for statistics are evaluated. The distinctive extent of long go genetic input observed for the Y chromosome shows that gene flow events to this area might have involved mainly males.

Curcumin Modulates 1,2-dibehenoyl-sn-glycero-3-phosphocholine (DBPC) Liposomes: Chitosan Oligosaccharide Lactate Influences Membrane Fluidity But Does Not Alter Phase Transition Temperature of DBPC Liposomes.

1,2-dibehenoyl-sn-glycero-3-phosphocholine (DBPC) is one of the important phospholipids found in cell membrane but not studied well. Importance of curcumin as a dietary supplement and for its medicinal properites is getting widely recoginsed. The present study for the first time explores the effect of curcumin on properties of DBPC liposomes by monitoring the fluorescence properties of curcumin. The phase transition temperature (Tm) of DBPC is assessed which confirms increase in curcumin concentration causes a slight drop in the Tm value. Chitosan is being applied for various drug delivery uses. The study establishes new insight on effect of chitosan oligosaccharide lactate on DBPC liposomes. It is found that in the absence of chitosan oligosaccharide lactate, curcumin partitions more strongly in the liquids crystalline phase than in the solid gel phase, however, the opposite result is obtained with the presence of chitosan oligosaccharide lactate which penetrates into the DBPC liposomes membranes at higher temperature, blocking thus the passage of curcumin into the lipid bilayer. However, addition of chitosan oligosaccharide lactate had no effect on the Tm. Fluorescence quenching study of curcumin establishes that the location of curcumin to be in the hydrophobic cavity of DBPC membrane.

Impact of socio-demographic and clinical characteristics on functional disability and health-related quality of life in patients with rheumatoid arthritis: a cross-sectional study from Palestine.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disorder, which has a significant impact on patients' health-related quality of life (HRQoL), and limits physical function as well as increases pain and fatigue. Therefore, this study aimed to evaluate the HRQoL and functional disability profile of patients with RA in Palestine to determine the socio-demographic and clinical features associated with low HRQoL and functional disability in patients with RA and to investigate the impact of drugs used on functional disability and HRQoL. METHODOLOGY: A cross-sectional, observational study conducted at rheumatology clinics in Northern West-Bank, Palestine (Alwatani Hospital-Nablus, Khalil Suleiman Hospital-Jenin, Thabet Thatbet Hospital-Tulkarem, and Darweesh Nazzal Hospital-Qalqilia). EuroQoL-5 Dimension scale (EQ-5D-5L) was used to evaluate HRQoL, Health Assessment Questionnaire, Disability Index (HAQ-DI) to evaluate the functional disability, and the Health Assessment Questionnaire pain visual analog scale (HAQ-VAS) to evaluate pain. RESULTS: 300 patients were included in the study, 229(76.3%) were females, the mean ± standard deviation age was 49 ± 13.10 years, and the median RA duration (lower-upper quartiles) was 6 (4-12) years. The median EQ-5D-5L index value and Euro QOL visual analogue scale (EQ-VAS) scores were 0.56 and 60, respectively. There was a significant strong positive correlation (R = 0.773; p < 0.001) between the EQ-5D-5L index values and the reported EQ-VAS scores. The median HAQ-DI and HAQ-VAS were 0.94 and 40, respectively. The results of multiple linear regression showed that treatment with biological DMARD (Etanercept), having work, higher income, absence of night pain, and absence of comorbid diseases were significantly associated with higher EQ-5D-5L index score (better HRQoL) and lower HAQ-DI scores (less disability). On the other hand, older age and the presence of morning stiffness were significantly associated with higher HAQ-DI scores (more disability). CONCLUSIONS: This study revealed the impact of treatment, clinical variables, and socio-demographic factors on disability and HRQoL in RA patients. Healthcare providers should be aware of the association between treatment with biological DMARD and improved HRQoL and functional status to make early interventions that reduce disability and improve HRQoL in susceptible patients.

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 nummularia (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.

Reactive Oxygen Species: Modulators of Phenotypic Switch of Vascular Smooth Muscle Cells.

Reactive oxygen species (ROS) are natural byproducts of oxygen metabolism in the cell. At physiological levels, they play a vital role in cell signaling. However, high ROS levels cause oxidative stress, which is implicated in cardiovascular diseases (CVD) such as atherosclerosis, hypertension, and restenosis after angioplasty. Despite the great amount of research conducted to identify the role of ROS in CVD, the image is still far from being complete. A common event in CVD pathophysiology is the switch of vascular smooth muscle cells (VSMCs) from a contractile to a synthetic phenotype. Interestingly, oxidative stress is a major contributor to this phenotypic switch. In this review, we focus on the effect of ROS on the hallmarks of VSMC phenotypic switch, particularly proliferation and migration. In addition, we speculate on the underlying molecular mechanisms of these cellular events. Along these lines, the impact of ROS on the expression of contractile markers of VSMCs is discussed in depth. We conclude by commenting on the efficiency of antioxidants as CVD therapies.

The Role of Epac in Cancer Progression.

Cancer continues to be a prime contributor to global mortality. Despite tremendous research efforts and major advances in cancer therapy, much remains to be learned about the underlying molecular mechanisms of this debilitating disease. A better understanding of the key signaling events driving the malignant phenotype of cancer cells may help identify new pharmaco-targets. Cyclic adenosine 3',5'-monophosphate (cAMP) modulates a plethora of biological processes, including those that are characteristic of malignant cells. Over the years, most cAMP-mediated actions were attributed to the activity of its effector protein kinase A (PKA). However, studies have revealed an important role for the exchange protein activated by cAMP (Epac) as another effector mediating the actions of cAMP. In cancer, Epac appears to have a dual role in regulating cellular processes that are essential for carcinogenesis. In addition, the development of Epac modulators offered new routes to further explore the role of this cAMP effector and its downstream pathways in cancer. In this review, the potentials of Epac as an attractive target in the fight against cancer are depicted. Additionally, the role of Epac in cancer progression, namely its effect on cancer cell proliferation, migration/metastasis, and apoptosis, with the possible interaction of reactive oxygen species (ROS) in these phenomena, is discussed with emphasis on the underlying mechanisms and pathways.

Antipsychotics drug aripiprazole as a lead against breast cancer cell line (MCF-7) in vitro.

Breast cancer is the second leading cause of death among women globally. The existing treatment options for breast cancer are largely associated with severe toxicities, and lower efficacies. Therefore, there is an urgent need for the development of non-toxic effective drugs against breast cancer. For this purpose, drug repositioning strategy was used to evaluate the anti-cancer potential of a library of heterocyclic drugs. The major advantage of drug repurposing is that the pharmacokinetic, pharmacodynamic, and toxicity profiles of drugs are well documented. In the current study, we screened 97 drugs of different chemical classes, and among them aripiprazole, an antipsychotic drug, was found to be sufficiently active against breast cancer cell line MCF-7. Aripiprazole showed a cytotoxicity (IC50 = 12.1 ± 0.40 µM) to MCF-7 cells, comparable to the standard anticancer drug doxorubicin (IC50 = 1.25 ± 0.34 µM). Aripiprazole was also found to be active against other cancer cell lines, including MDA-MB-231 (IC50 = 19.83 ± 0.27 µM), AU565 (IC50 = 18.02 ± 0.44 µM), and BT-474 (IC50 = 36.42 ± 0.12 µM). Aripiprazole significantly inhibited the cell cycle progression at subG0G1 phase, and enhanced apoptosis in MCF-7 breast cancer cells. The drug was also able to significantly increase the nuclear condensation, and modulated the expression of certain genes involved in breast cancer, such as caspases 3, and 9, BAK-1, C-MYC, BCL2L1, BCL-10, and BCL-2. Further studies are needed to explore the effect of aripiprazole on intrinsic and extrinsic pathways of apoptosis in cancer cells.

EPAC in Vascular Smooth Muscle Cells.

Vascular smooth muscle cells (VSMCs) are major components of blood vessels. They regulate physiological functions, such as vascular tone and blood flow. Under pathological conditions, VSMCs undergo a remodeling process known as phenotypic switching. During this process, VSMCs lose their contractility and acquire a synthetic phenotype, where they over-proliferate and migrate from the tunica media to the tunica interna, contributing to the occlusion of blood vessels. Since their discovery as effector proteins of cyclic adenosine 3',5'-monophosphate (cAMP), exchange proteins activated by cAMP (EPACs) have been shown to play vital roles in a plethora of pathways in different cell systems. While extensive research to identify the role of EPAC in the vasculature has been conducted, much remains to be explored to resolve the reported discordance in EPAC's effects. In this paper, we review the role of EPAC in VSMCs, namely its regulation of the vascular tone and phenotypic switching, with the likely involvement of reactive oxygen species (ROS) in the interplay between EPAC and its targets/effectors.