MyMedR

Displaying all 7 publications

Abstract:

Sort:

Fulltext Molecular mechanistic pathways underlying the anticancer therapeutic efficiency of romidepsin

El Omari N, Lee LH, Bakrim S, Makeen HA, Alhazmi HA, Mohan S, et al.

Biomed Pharmacother, 2023 Aug;164:114774.
PMID: 37224749 DOI: 10.1016/j.biopha.2023.114774

Romidepsin, also known as NSC630176, FR901228, FK-228, FR-901228, depsipeptide, or Istodax®, is a natural molecule produced by the Chromobacterium violaceum bacterium that has been approved for its anti-cancer effect. This compound is a selective histone deacetylase (HDAC) inhibitor, which modifies histones and epigenetic pathways. An imbalance between HDAC and histone acetyltransferase can lead to the down-regulation of regulatory genes, resulting in tumorigenesis. Inhibition of HDACs by romidepsin indirectly contributes to the anticancer therapeutic effect by causing the accumulation of acetylated histones, restoring normal gene expression in cancer cells, and promoting alternative pathways, including the immune response, p53/p21 signaling cascades, cleaved caspases, poly (ADP-ribose) polymerase (PARP), and other events. Secondary pathways mediate the therapeutic action of romidepsin by disrupting the endoplasmic reticulum and proteasome and/or aggresome, arresting the cell cycle, inducing intrinsic and extrinsic apoptosis, inhibiting angiogenesis, and modifying the tumor microenvironment. This review aimed to highlight the specific molecular mechanisms responsible for HDAC inhibition by romidepsin. A more detailed understanding of these mechanisms can significantly improve the understanding of cancer cell disorders and pave the way for new therapeutic approaches using targeted therapy.
Fulltext Polymorphism of HLA and Susceptibility of Breast Cancer

Aboulaghras S, Khalid A, Makeen HA, Alhazmi HA, Albratty M, Mohan S, et al.

Front Biosci (Landmark Ed), 2024 Feb 05;29(2):55.
PMID: 38420797 DOI: 10.31083/j.fbl2902055

Breast cancer (BC) is the second most common malignancy in the world. Numerous studies have demonstrated the association between human leukocyte antigen (HLA) and cancer. The occurrence and development of BC are closely linked to genetic factors. Human leukocyte antigens G and E (HLA-G and HLA-E) are non-classical major histocompatibility complex (MHC) class I molecules. These molecules play an important role in immune surveillance by inhibiting the cytotoxic and natural killer T cells responsible for immune escape. The expression of HLA-G and HLA-E has been associated with several diseases, including tumors. The HLA system plays a key role in the escape of tumor cells from immune surveillance. This review aims to determine the correlation between BC susceptibility and HLA markers specific HLA alleles such as HLA-B07, HLA-DRB111, HLA-DRB113, and HLA-DRB115 are associated with an increased risk of developing BC. Furthermore, HLA-G mutations have been attributed to an elevated likelihood of metastasis in BC patients. Understanding the complex associations between the HLA system and BC development is critical for developing novel cancer prevention, detection, and treatment strategies. This review emphasizes the importance of analyzing HLA polymorphisms in the management of BC patients, as well as the urgent need for further research in this area.
Fulltext Clinical applications and mechanism insights of natural flavonoids against type 2 diabetes mellitus

Bouyahya A, Balahbib A, Khalid A, Makeen HA, Alhazmi HA, Albratty M, et al.

Heliyon, 2024 May 15;10(9):e29718.
PMID: 38694079 DOI: 10.1016/j.heliyon.2024.e29718

Diabetes is a complex disease that affects a large percentage of the world's population, and it is associated with several risk factors. Self-management poses a significant challenge, but natural sources have shown great potential in providing effective glucose reducing solutions. Flavonoids, a class of bioactive substances found in different natural sources including medicinal plants, have emerged as promising candidates in this regard. Indeed, several flavonoids, including apigenin, arbutin, catechins, and cyanidin, have demonstrated remarkable anti-diabetic properties. The clinical effectiveness of these flavonoids is linked to their potential to decrease blood glucose concentration and increase insulin concentration. Thus, the regulation of certain metabolic pathways such as glycolysis and neoglycogenesis has also been demonstrated. In vitro and in vivo investigations revealed different mechanisms of action related to flavonoid compounds at subcellular, cellular, and molecular levels. The main actions reside in the activation of glycolytic signaling pathways and the inhibition of signaling that promotes glucose synthesis and storage. In this review, we highlight the clinical efficiency of natural flavonoids as well as the molecular mechanisms underlying this effectiveness.
Stochasticity of anticancer mechanisms underlying clinical effectiveness of vorinostat

El Omari N, Khalid A, Makeen HA, Alhazmi HA, Albratty M, Mohan S, et al.

Heliyon, 2024 Jun 30;10(12):e33052.
PMID: 39021957 DOI: 10.1016/j.heliyon.2024.e33052

The Food and Drug Administration (FDA) has approved vorinostat, also called Zolinza®, for its effectiveness in fighting cancer. This drug is a suberoyl-anilide hydroxamic acid belonging to the class of histone deacetylase inhibitors (HDACis). Its HDAC inhibitory potential allows it to accumulate acetylated histones. This, in turn, can restore normal gene expression in cancer cells and activate multiple signaling pathways. Experiments have proven that vorinostat induces histone acetylation and cytotoxicity in many cancer cell lines, increases the level of p21 cell cycle proteins, and enhances pro-apoptotic factors while decreasing anti-apoptotic factors. Additionally, it regulates the immune response by up-regulating programmed death-ligand 1 (PD-L1) and interferon gamma receptor 1 (IFN-γR1) expression, and can impact proteasome and/or aggresome degradation, endoplasmic reticulum function, cell cycle arrest, apoptosis, tumor microenvironment remodeling, and angiogenesis inhibition. In this study, we sought to elucidate the precise molecular mechanism by which Vorinostat inhibits HDACs. A deeper understanding of these mechanisms could improve our understanding of cancer cell abnormalities and provide new therapeutic possibilities for cancer treatment.
Fulltext The association of dietary behaviors and practices with overweight and obesity parameters among Saudi university students

Syed NK, Syed MH, Meraya AM, Albarraq AA, Al-Kasim MA, Alqahtani S, et al.

PLoS One, 2020;15(9):e0238458.
PMID: 32911507 DOI: 10.1371/journal.pone.0238458

BACKGROUND: Western dietary habits, coupled with a sedentary lifestyle, are potential contributors to the prevalence and rapid increase in the incidence of obesity in Saudi Arabia. This study aimed to investigate the association between students' weight status and their eating behaviors and practices. Another aim was to assess students' awareness of the health risks associated with obesity.
METHODS: A cross-sectional survey was conducted among a sample of 416 (53% male and 47% female) undergraduate students, aged 18-26 years old, between January 6 and April 6, 2019, from colleges of Health Sciences at Jazan University in the Kingdom of Saudi Arabia (K.S.A). Students completed a self-administered questionnaire and recorded their measured anthropometric parameters.
RESULTS: The prevalence of overweight (20.4%) and obesity (14.9%) were relatively high among the participants. There were statistically significant associations between Body Mass Index (BMI) and the different settings of food consumption (i.e., dining on a table (or) in the Islamic way: squatting on the ground) (p<0.001)). BMI was also associated with students' dietary habits regarding consuming food, snacks, and drinking carbonated beverages while watching television (p<0.001), as well as consuming the same pattern of food/drink while watching television, playing video games on mobile phones or computers (p<0.001). Nearly most of the students were oblivious to the fact that metabolic syndrome, reproductive disorders, respiratory disorders along with liver and gallbladder diseases are some of the health risks associated with obesity.
CONCLUSION: The prevalence of obesity and overweight were reasonably high in our study sample and were affected by several factors related to students' eating behaviors and practices. This warrants the need for rigorous and frequent health education interventions on healthy eating behaviors, dietary practices, with an emphasis on the importance of adopting an active, healthy lifestyle.
Role of Medicinal plant-derived Nutraceuticals as a potential target for the treatment of breast cancer

Alharbi KS, Almalki WH, Makeen HA, Albratty M, Meraya AM, Nagraik R, et al.

J Food Biochem, 2022 Dec;46(12):e14387.
PMID: 36121313 DOI: 10.1111/jfbc.14387

Breast cancer (BC) is one of the most challenging cancers to treat, accounting for many cancer-related deaths. Over some years, chemotherapy, hormone treatment, radiation, and surgeries have been used to treat cancer. Unfortunately, these treatment options are unsuccessful due to crucial adverse reactions and multidrug tolerance/resistance. Although it is clear that substances in the nutraceuticals category have a lot of anti-cancer activity, using a supplementary therapy strategy, in this case, could be very beneficial. Nutraceuticals are therapeutic agents, which are nutrients that have drug-like characteristics and can be used to treat diseases. Plant nutraceuticals categorized into polyphenols, terpenoids, vitamins, alkaloids, and flavonoids are part of health food products, that have great potential for combating BC. Nutraceuticals can reduce BC's severity, limit malignant cell growth, and modify cancer-related mechanisms. Nutraceuticals acting by attenuating Hedgehog, Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), Notch, and Wnt/β-catenin signaling are the main pathways in controlling the self-renewal of breast cancer stem cells (BCSCs). This article reviews some important nutraceuticals and their modes of action, which can be very powerful versus BC. PRACTICAL APPLICATIONS: Nutraceuticals' importance to the control and diagnosis of breast cancer is undeniable and cannot be overlooked. Natural dietary compounds have a wide range of uses and have been used in traditional medicine. In addition, these natural chemicals can enhance the effectiveness of other traditional medicines. They may also be used as a treatment process independently because of their capacity to affect several cancer pathways. This study highlights a variety of natural chemicals, and their mechanisms of action, routes, synergistic effects, and future potentials are all examined.
Fulltext Natural bioactive compounds targeting DNA methyltransferase enzymes in cancer: Mechanisms insights and efficiencies

Aanniz T, Bouyahya A, Balahbib A, El Kadri K, Khalid A, Makeen HA, et al.

Chem Biol Interact, 2024 Apr 01;392:110907.
PMID: 38395253 DOI: 10.1016/j.cbi.2024.110907

The regulation of gene expression is fundamental to health and life and is essentially carried out at the promoter region of the DNA of each gene. Depending on the molecular context, this region may be accessible or non-accessible (possibility of integration of RNA polymerase or not at this region). Among enzymes that control this process, DNA methyltransferase enzymes (DNMTs), are responsible for DNA demethylation at the CpG islands, particularly at the promoter regions, to regulate transcription. The aberrant activity of these enzymes, i.e. their abnormal expression or activity, can result in the repression or overactivation of gene expression. Consequently, this can generate cellular dysregulation leading to instability and tumor development. Several reports highlighted the involvement of DNMTs in human cancers. The inhibition or activation of DNMTs is a promising therapeutic approach in many human cancers. In the present work, we provide a comprehensive and critical summary of natural bioactive molecules as primary inhibitors of DNMTs in human cancers. The active compounds hold the potential to be developed as anti-cancer epidrugs targeting DNMTs.