Cannabis and cancer: unveiling the potential of a green ally in breast, colorectal, and prostate cancer.

Cancer comes in second place on the list of causes of death worldwide. In 2018, the 5-year prevalence of breast cancer (BC), prostate cancer (PC), and colorectal cancer (CRC) were 30%, 12.3%, and 10.9%, respectively. Cannabinoids are chemicals derived from the Cannabis sativa plant; the most investigated cannabinoids are cannabinol, delta 9-tetrahydrocannabinol (Δ9-THC), and cannabidiol. In humans, the endogenous endocannabinoid system consists of endocannabinoids, cannabinoids receptors (CBs), and enzymes that degrade the endocannabinoids. In this review, we will review the most recent literature for evidence that discusses the role of cannabis in the treatment of the three types of neoplasms mentioned. Studies have proved that BC cells express CB receptors; many in-vivo studies showed that cannabinoids cause apoptosis and inhibit proliferation and migration. Also, researchers found that treating BC mice with THC and JWH-133 (CB2 receptor agonist) slowed the tumor growth. Regarding CRC, cannabidiol was found to decrease the viability of chemotherapy-resistant CRC cells and inhibit metastasis by antagonizing the G-protein-coupled receptor 55 (GPR55; a novel cannabinoid receptor) necessary for metastasis. Moreover, cannabidiol had anti-angiogenetic effects by reducing the expression of vascular endothelial growth factor (VEGF) in addition to anti-inflammatory effects. Finally, studies demonstrated that PC cells highly express CB1 and CB2 receptors and that cannabinoids are capable of inhibiting the release of exosomes and microvesicles related to cancer progression. Cannabinoids also have antiproliferative, anti-invasive, anti-fibroblastic, cell cycle arrest, and proapoptotic effects on PC cells.

Factors associated with knowledge and awareness of stroke in the Iraqi population: a cross-sectional study.

Introduction: Stroke is a highly prevalent condition with high rates of death and disability in Iraq and around the world. Knowledge of stroke and its associated risk factors is essential for disease prevention and rapid response when confronted with a stroke patient. Purpose: The purpose of this study is to assess stroke knowledge and identify factors associated with awareness among the Iraqi public. Material and methods: A questionnaire-based, cross-sectional survey was conducted on the Iraqi population. The self-administered online questionnaire contained three sections. The study got ethical approval from the Research Ethics Committee at the University of Baghdad. Results: The results showed that 26.8% of the participants reported knowledge regarding identifying all risk factors. In addition, 18.4% and 34.8% of the participants recognized all symptoms and mentioned all possible consequences of stroke, respectively. Previous medical history with chronic diseases had essential relationships with the response when faced with a person having an acute stroke. In addition, there was a significant relationship between gender, smoking history, and identification of early stroke symptoms. Conclusion: There was a lack of knowledge about risk factors for stroke among the participants. There is a need for an awareness program among the Iraqi people to raise their understanding of stroke that can reduce stroke mortality and morbidity.

Anti-Proliferative Effect of Potential LSD1/CoREST Inhibitors Based on Molecular Dynamics Model for Treatment of SH-SY5Y Neuroblastoma Cancer Cell Line.

BACKGROUND: Lysine-specific demethylase is a demethylase enzyme that can remove methyl groups from histones H3K4me1/2 and H3K9me1/2. It is expressed in many cancers, where it impedes differentiation and contributes to cancer cell proliferation, cell metastasis and invasiveness, and is associated with inferior prognosis. LSD1 is associated with its corepressor protein CoREST, and utilizes tetrahydrofolate as a cofactor to accept CH2 from the demethylation process. The fact that the cofactor is best bound to the active site inspired us to explore its interactions to LSD1/CoREST enzyme complex utilizing molecular dynamics simulation, which aids designing novel and potent inhibitors. OBJECTIVE: In this study we minted to identify a new potential LSD1/CoREST inhibitors and test the potency and the safety of such inhibitors against human neuroblastoma and fibroblast cells lines. METHODS: We have implemented a previously derived model from the molecular dynamics simulation study and the key contacts to the active site in a subsequent structure based drug design and in-silico screening, which revealed a number of potential inhibitors toward LSD1/CoREST complex. The anti-proliferative activities of the identified compounds will be tested against neuroblastoma SH-SY5Y cancer cell line which known to highly express LSD1/CoREST complex. RESULTS: In-silico mining on National Cancer Institute (NCI) database identified 55 promising and structurally diverse inhibitors. Applying the abovementioned molecular modeling procedure yielded four compounds of LSD1/CoREST inhibiters with IC50 < 2µM. The four lead compounds were tested against SH-SY5Y neuroblastoma cell line that known to express high level of LSD1 and illustrated a potent activity with an IC50 ranging from 0.195 to 1.52µM. To estimate the toxicity of the selective leads, they were tested against normal fibroblast cells and scored a relatively high IC50 ranging from 0.303 to ≥ 100µM. CONCLUSION: Our model revealed promising inhibitors that can be used in treating cancers that overexpress the LSD1 enzyme such as the SH-SY5Y neuroblastoma.

Oral contraceptive and breast cancer: do benefits outweigh the risks? A case - control study from Jordan.

BACKGROUND: Oral contraceptives (OCs) use has been linked to increased risk of breast cancer (BC) in several reports from the world. Limited number of similar studies have been conducted in the Middle Eastern female population. This study aimed to explore any possible correlation between the contemporary and duration of OCs use among Jordanian women and the risk of breast cancer. METHODS: A case control study was conducted in 450 Jordanian women (225 as cases and 225 as controls), aged 18 to 65. Chi-square test was used to study the association between risk of breast cancer and different factors. Mann Whitney-U test was employed to evaluate the relation between time-dependent risk factor and breast cancer. RESULTS: Our results indicated that regular use of OCs exhibited association with increased risk of breast cancer (OR = 2.25, 95% CI 1.34-2.79; p = 0.002), while the duration of OCs use was not associated with the increased risk of breast cancer (p > 0.05). In addition, other factors demonstrated significant association with the increased risk of breast cancer such as age at puberty, age at menopause, previous pregnancies, menopausal status, and family history of cancer. CONCLUSIONS: regular use of OCs may be associated with increased risk of breast cancer in Jordanian women. A larger sample size in multi-center setting study is required to confirm this finding among the Jordanian female population.

Reactive Oxygen Species: the Dual Role in Physiological and Pathological Conditions of the Human Body.

Reactive oxygen species (ROS) are well-known for playing a dual role as destructive and constructive species. Indeed, ROS are engaged in many redox-governing activities of the cells for the preservation of cellular homeostasis. However, its overproduction has been reported to result in oxidative stress, which is considered as a deleterious process, and is involved in the damage of cell structures that causes various diseased states. This review provides a concise view on some of the current research published in this topic for an improved understanding of the key roles of ROS in diverse conditions of health and disease. Previous research demonstrated that ROS perform as potential signaling molecules to control several normal physiological functions at the cellular level. Additionally, there is a growing body of evidence supporting the role of ROS in various pathological states. The binary nature of ROS with their profitable and injurious characteristics indicates the complexities of their specific roles at a biological compartment and the difficulties in establishing convenient intervention procedures to treat ROS-related diseases.

Phenolic Compounds and Bioactivity of Cytisus villosus Pourr.

The present study focuses on the chemical composition, antioxidant, antimicrobial, and antiproliferative activities of the ethyl acetate and aqueous extracts obtained from the aerial parts of Cytisus villosus Pourr. HPLC-DAD-ESI/MSn was used to identify the phenolic compounds, being (epi)gallocatechin dimer the major compound (111 ± 5 µg/g·dw) in the aqueous extract, while myricetin-O-rhamnoside (226 ± 9 µg/g·dw) was the main molecule in the ethyl acetate extract. Both extracts exhibited good scavenging activities against DPPH radical (EC50 µg/mL of 59 ± 2 and 31 ± 2 for aqueous and ethyl acetate extracts, respectively). However, the ethyl acetate extract demonstrated more potent quenching activities than the aqueous extract. The antimicrobial activities were assessed on selected Gram-positive (Staphylococcus epidermidis) and Gram-negative (Escherichia coli and Pseudomonas aeruginosa) bacteria, as well as on pathogenic fungus Candida glabrata. The extracts possessed selective and potent antimicrobial activities against the Gram-positive bacterium (IC50 of 186 ± 9 µg/mL and 92 ± 3 µg/mL for aqueous and ethyl acetate extracts, respectively). Finally, C. villosus extracts were evaluated for their antiproliferative potential on three human cancer cell lines representing breast and colon cancers. Although both extracts demonstrated sufficient growth inhibition of the three different cell lines, the ethyl acetate extract exhibited higher activity (LD50 values of 1.57 ± 0.06 mg/mL, 2.2 ± 0.1 mg/mL, and 3.2 ± 0.2 mg/mL for T47D, MCF-7, and HCT-116 cell lines). Both the extracts obtained from the aerial parts of C. villosus revealed very promising results and could be applied as functional agents in the food, pharmaceutical, and cosmeceutical industries.

Chemical composition, antioxidant, antimicrobial and Antiproliferative activities of essential oil of Mentha spicata L. (Lamiaceae) from Algerian Saharan atlas.

BACKGROUND: Mentha spicata (M. spicata) is a member of Lamiaceae that spreads mainly in the temperate and sub-temperate zones of the world. It is considered as a rich source of essential oils, which is widely used in pharmaceutical industries and food production. The objectives of the current study were to evaluate chemical composition, antioxidant, antimicrobial and antiproliferative activities associated with the essential oil of M. spicata cultivated in Algerian Saharan Atlas. METHODS: The aerial parts of M. spicata were subjected to hydrodistillation to produce the oil. Chemical identification of the oil composition was conducted by GC and GC-MS analyses. The antioxidant activity of the hydrodistilled oil was studied using DPPH, ABTS radical scavenging and ferric-reducing power assay. Antimicrobial potential was characterized against two microorganisms, signifying Gram positive, and Gram negative bacteria, and one Candida species. The microdilution method was employed to determine the minimum inhibitory concentration (MIC). The oil's antiproliferative effects against three human tumor cell lines were also investigated using the MTT assay, and the toxic doses that yielded 50% reduction of cell viability (LD50) were reported. RESULTS: Chemical analysis of the essential oil composition revealed 44 unique compounds with oxygenated monoterpenes (67.2%), followed by monoterpene hydrocarbons (20.8%), as the most abundant chemical components. Essential oil of M. spicata demonstrated moderate antioxidant activities as well as moderate to weak antimicrobial activities with best susceptibility observed for Gram positive bacteria towards the oil. In addition, anticancer activities that are associated with the oil against three human cancer cell lines were observed with LD50 values of 324 µg/mL, 279 µg/mL, 975 µg/mL against T47D, HCT-116 and MCF-7 cell lines, respectively. CONCLUSION: The results suggest that M. spicata essential oil may have potential value as a bioactive oil, for nutraceutical and medical applications, with its antioxidant, antimicrobial and antiproliferative activities.

Glucose Deprivation Enhances the Antiproliferative Effects of Oral Hypoglycemic Biguanides in Different Molecular Subtypes of Breast Cancer: an in Vitro Study.

Extensive in vitro studies have been conducted to evaluate the anticancer activity of oral hypoglycemic agents. Many of these studies experienced detrimental limitations, since they were conducted on cancer cells commonly grown in culture media consisting of extremely high concentrations of growth factors and glucose. The present study was aimed at exploring the antiproliferative effects of the commonly studied metformin and the less frequently reported phenformin oral hypoglycemic agents on different molecular subtypes of breast cancer under rich glucose and glucose deprived conditions. Our results indicate that under glucose deprived conditions, which better reflect the factual glucose-starved solid tumors in vivo, biguanides exert more antiproliferative activities against the three molecular subtypes of breast cancer cell lines examined in this study. In addition, the observed antiproliferative activities of biguanides appear to be mediated by apoptosis induction in breast cancer cells. This induction is significantly augmented under glucose deprived conditions.