Molecular Mechanisms Underlying Cancer Preventive and Therapeutic Potential of Algal Polysaccharides

2019 ◽  
Vol 25 (11) ◽  
pp. 1210-1235 ◽  
Author(s):  
Soraya Sajadimajd ◽  
Saeideh Momtaz ◽  
Pouya Haratipour ◽  
Fardous F. El-Senduny ◽  
Amin Iran Panah ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Anticancer Agents ◽  
Recent Progress ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Sulfated Polysaccharides ◽  
Cochrane Library ◽  
Therapeutic Effects ◽  
Cancer Management ◽  
Algal Polysaccharides

Background: Algal polysaccharide and oligosaccharide derivatives have been shown to possess a variety of therapeutic potentials and drug delivery applications. Algal polysaccharides contain sulfated sugar monomers derived from seaweed including brown, red, and green microalgae. Here, in this review, the recent progress of algal polysaccharides’ therapeutic applications as anticancer agents, as well as underlying cellular and molecular mechanisms was investigated. Moreover, recent progress in the structural chemistry of important polysaccharides with anticancer activities were illustrated. Methods: Electronic databases including “Scopus”, “PubMed”, and “Cochrane library” were searched using the keywords “cancer”, or “tumor”, or “malignancy” in title/abstract, along with “algae”, or “algal” in the whole text until July 2018. Only English language papers were included. Results: The most common polysaccharides involved in cancer management were sulfated polysaccharides, Fucoidans, Carageenans, and Ulvan from different species of algae that have been recognized in vitro and in vivo. The underlying anticancer mechanisms of algal polysaccharides included induction of apoptosis, cell cycle arrest, modulation of transduction signaling pathways, suppression of migration and angiogenesis, as well as activation of immune responses and antioxidant system. VEGF/VEGFR2, TGFR/Smad/Snail, TLR4/ROS/ER, CXCL12/ CXCR4, TGFR/Smad7/Smurf2, PI3K/AKT/mTOR, PBK/TOPK, and β-catenin/Wnt are among the main cellular signaling pathways which have a key role in the preventive and therapeutic effects of algal polysaccharides against oncogenesis. Conclusion: Algal polysaccharides play a crucial role in the management of cancer and may be considered the next frontier in pharmaceutical research. Further well-designed clinical trials are mandatory to evaluate the efficacy and safety of algal polysaccharides in patients with cancer.

scholarly journals β-Caryophyllene, A Natural Dietary CB2 Receptor Selective Cannabinoid can be a Candidate to Target the Trinity of Infection, Immunity, and Inflammation in COVID-19

2021 ◽  
Vol 12 ◽  
Author(s):  
Niraj Kumar Jha ◽  
Charu Sharma ◽  
Hebaallah Mamdouh Hashiesh ◽  
Seenipandi Arunachalam ◽  
MF Nagoor Meeran ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Immune Modulation ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Endocannabinoid System ◽  
Therapeutic Effects ◽  
Peroxisome Proliferator ◽  
Cb2 Receptors ◽  
Anti Inflammatory

Coronavirus disease (COVID-19), caused by novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an ongoing pandemic and presents a public health emergency. It has affected millions of people and continues to affect more, despite tremendous social preventive measures. Identifying candidate drugs for the prevention and treatment of COVID-19 is crucial. The pathogenesis and the complications with advanced infection mainly involve an immune-inflammatory cascade. Therefore, therapeutic strategy relies on suppressing infectivity and inflammation, along with immune modulation. One of the most promising therapeutic targets for the modulation of immune-inflammatory responses is the endocannabinoid system, particularly the activation of cannabinoid type 2 receptors (CB2R), a G-protein coupled receptor which mediates the anti-inflammatory properties by modulating numerous signaling pathways. To pharmacologically activate the CB2 receptors, a naturally occurring cannabinoid ligand, beta-caryophyllene (BCP), received attention due to its potent anti-inflammatory, antiviral, and immunomodulatory properties. BCP is recognized as a full selective functional agonist on CB2 receptors and produces therapeutic effects by activating CB2 and the nuclear receptors, peroxisome proliferator-activated receptors (PPARs). BCP is regarded as the first dietary cannabinoid with abundant presence across cannabis and non-cannabis plants, including spices and other edible plants. BCP showed tissue protective properties and favorably modulates numerous signaling pathways and inhibits inflammatory mediators, including cytokines, chemokines, adhesion molecules, prostanoids, and eicosanoids. Based on its pharmacological properties, molecular mechanisms, and the therapeutic potential of BCP as an immunomodulator, anti-inflammatory, organ-protective, and antiviral, we hypothesize that BCP could be a promising therapeutic and/or preventive candidate to target the triad of infection, immunity, and inflammation in COVID-19. In line with numerous studies that proposed the potential of cannabinoids in COVID-19, BCP may be a novel candidate compound for pharmaceutical and nutraceutical development due to its unique functional receptor selectivity, wide availability and accessibility, dietary bioavailability, nonpsychoactivity, and negligible toxicity along with druggable properties, including favorable pharmacokinetic and physicochemical properties. Based on reasonable pharmacological mechanisms and therapeutic properties, we speculate that BCP has potential to be investigated against COVID-19 and will inspire further preclinical and clinical studies.

Classic and Novel Signaling Pathways Involved in Cancer: Targeting the NF-κB and Syk Signaling Pathways

2019 ◽  
Vol 14 (3) ◽  
pp. 219-225 ◽  
Author(s):  
Cong Tang ◽  
Guodong Zhu
Keyword(s):  
Cancer Therapy ◽  
Tyrosine Kinase ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Cell Receptor ◽  
Transmembrane Receptors ◽  
Biological Responses ◽  
Different Types

The nuclear factor kappa B (NF-κB) consists of a family of transcription factors involved in the regulation of a wide variety of biological responses. Growing evidence support that NF-κB plays a major role in oncogenesis as well as its well-known function in the regulation of immune responses and inflammation. Therefore, we made a review of the diverse molecular mechanisms by which the NF-κB pathway is constitutively activated in different types of human cancers and the potential role of various oncogenic genes regulated by this transcription factor in cancer development and progression. We also discussed various pharmacological approaches employed to target the deregulated NF-κB signaling pathway and their possible therapeutic potential in cancer therapy. Moreover, Syk (Spleen tyrosine kinase), non-receptor tyrosine kinase which mediates signal transduction downstream of a variety of transmembrane receptors including classical immune-receptors like the B-cell receptor (BCR), which can also activate the inflammasome and NF-κB-mediated transcription of chemokines and cytokines in the presence of pathogens would be discussed as well. The highlight of this review article is to summarize the classic and novel signaling pathways involved in NF-κB and Syk signaling and then raise some possibilities for cancer therapy.

scholarly journals Abnormal Iron and Lipid Metabolism Mediated Ferroptosis in Kidney Diseases and Its Therapeutic Potential

Metabolites ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 58
Author(s):  
Xiaoqin Zhang ◽  
Xiaogang Li
Keyword(s):  
Kidney Disease ◽  
Signaling Pathways ◽  
Metabolic Pathways ◽  
Molecular Mechanisms ◽  
Unsaturated Fatty Acids ◽  
Therapeutic Potential ◽  
Kidney Diseases ◽  
Intracellular Iron ◽  
Metabolic Signaling ◽  
Iron Regulatory Proteins

Ferroptosis is a newly identified form of regulated cell death driven by iron-dependent phospholipid peroxidation and oxidative stress. Ferroptosis has distinct biological and morphology characteristics, such as shrunken mitochondria when compared to other known regulated cell deaths. The regulation of ferroptosis includes different molecular mechanisms and multiple cellular metabolic pathways, including glutathione/glutathione peroxidase 4(GPX4) signaling pathways, which are involved in the amino acid metabolism and the activation of GPX4; iron metabolic signaling pathways, which are involved in the regulation of iron import/export and the storage/release of intracellular iron through iron-regulatory proteins (IRPs), and lipid metabolic signaling pathways, which are involved in the metabolism of unsaturated fatty acids in cell membranes. Ferroptosis plays an essential role in the pathology of various kidneys diseases, including acute kidney injury (AKI), chronic kidney disease (CKD), autosomal dominant polycystic kidney disease (ADPKD), and renal cell carcinoma (RCC). Targeting ferroptosis with its inducers/initiators and inhibitors can modulate the progression of kidney diseases in animal models. In this review, we discuss the characteristics of ferroptosis and the ferroptosis-based mechanisms, highlighting the potential role of the main ferroptosis-associated metabolic pathways in the treatment and prevention of various kidney diseases.

scholarly journals Targeting Multiple Signaling Pathways in Cancer: The Rutin Therapeutic Approach

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2276 ◽  
Author(s):  
Zeinab Nouri ◽  
Sajad Fakhri ◽  
Keyvan Nouri ◽  
Carly E. Wallace ◽  
Mohammad Hosein Farzaei ◽  
...  
Keyword(s):  
Medicinal Plants ◽  
Signaling Pathways ◽  
Anticancer Agents ◽  
Molecular Mechanisms ◽  
Critical Evaluation ◽  
B Cell Lymphoma ◽  
Nuclear Factor Κb ◽  
Anticancer Effects ◽  
Factor Α ◽  
Endothelial Growth Factor

Multiple dysregulated signaling pathways are implicated in the pathogenesis of cancer. The conventional therapies used in cancer prevention/treatment suffer from low efficacy, considerable toxicity, and high cost. Hence, the discovery and development of novel multi-targeted agents to attenuate the dysregulated signaling in cancer is of great importance. In recent decades, phytochemicals from dietary and medicinal plants have been successfully introduced as alternative anticancer agents due to their ability to modulate numerous oncogenic and oncosuppressive signaling pathways. Rutin (also known as rutoside, quercetin-3-O-rutinoside and sophorin) is an active plant-derived flavonoid that is widely distributed in various vegetables, fruits, and medicinal plants, including asparagus, buckwheat, apricots, apples, cherries, grapes, grapefruit, plums, oranges, and tea. Rutin has been shown to target various inflammatory, apoptotic, autophagic, and angiogenic signaling mediators, including nuclear factor-κB, tumor necrosis factor-α, interleukins, light chain 3/Beclin, B cell lymphoma 2 (Bcl-2), Bcl-2 associated X protein, caspases, and vascular endothelial growth factor. A comprehensive and critical analysis of the anticancer potential of rutin and associated molecular targets amongst various cancer types has not been performed previously. Accordingly, the purpose of this review is to present an up-to-date and critical evaluation of multiple cellular and molecular mechanisms through which the anticancer effects of rutin are known to be exerted. The current challenges and limitations as well as future directions of research are also discussed.

scholarly journals Targeting Autophagy with Natural Compounds in Cancer: A Renewed Perspective from Molecular Mechanisms to Targeted Therapy

2021 ◽  
Vol 12 ◽  
Author(s):  
Qiang Xie ◽  
Yi Chen ◽  
Huidan Tan ◽  
Bo Liu ◽  
Ling-Li Zheng ◽  
...  
Keyword(s):  
Natural Products ◽  
Cancer Therapy ◽  
Signaling Pathways ◽  
Small Molecule ◽  
Molecular Mechanisms ◽  
Biological Activities ◽  
Natural Compounds ◽  
Therapeutic Effects ◽  
Therapeutic Benefits ◽  
Small Molecule Drugs

Natural products are well-characterized to have pharmacological or biological activities that can be of therapeutic benefits for cancer therapy, which also provide an important source of inspiration for discovery of potential novel small-molecule drugs. In the past three decades, accumulating evidence has revealed that natural products can modulate a series of key autophagic signaling pathways and display therapeutic effects in different types of human cancers. In this review, we focus on summarizing some representative natural active compounds, mainly including curcumin, resveratrol, paclitaxel, Bufalin, and Ursolic acid that may ultimately trigger cancer cell death through the regulation of some key autophagic signaling pathways, such as RAS-RAF-MEK-ERK, PI3K-AKT-mTOR, AMPK, ULK1, Beclin-1, Atg5 and p53. Taken together, these inspiring findings would shed light on exploiting more natural compounds as candidate small-molecule drugs, by targeting the crucial pathways of autophagy for the future cancer therapy.

Cordycepin in Anticancer Research: Molecular Mechanism of Therapeutic Effects

2020 ◽  
Vol 27 (6) ◽  
pp. 983-996 ◽  
Author(s):  
Md. Asaduzzaman Khan ◽  
Mousumi Tania
Keyword(s):  
Anticancer Activity ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Cancer Drug ◽  
Therapeutic Effects ◽  
Anticancer Activities ◽  
Cancer Cell Growth ◽  
Ongoing Research

Background: Cordycepin is a nucleotide analogue from Cordyceps mushrooms, which occupies a notable place in traditional medicine. Objective: In this review article, we have discussed the recent findings on the molecular aspects of cordycepin interactions with its recognized cellular targets, and possible mechanisms of its anticancer activity. Methods: We have explored databases like pubmed, google scholar, scopus and web of science for the update information on cordycepin and mechanisms of its anticancer activity, and reviewed in this study. Results: Cordycepin has been widely recognized for its therapeutic potential against many types of cancers by various mechanisms. More specifically, cordycepin can induce apoptosis, resist cell cycle and cause DNA damage in cancer cells, and thus kill or control cancer cell growth. Also cordycepin can induce autophagy and modulate immune system. Furthermore, cordycepin also inhibits tumor metastasis. Although many success stories of cordycepin in anticancer research in vitro and in animal model, and there is no successful clinical trial yet. Conclusion: Ongoing research studies have reported highly potential anticancer activities of cordycepin with numerous molecular mechanisms. The in vitro and in vivo success of cordycepin in anticancer research might influence the clinical trials of cordycepin, and this molecule might be used for development of future cancer drug.

Anti-Tumor Effects of Osthole on Different Malignant Tissues: A Review of Molecular Mechanisms

2020 ◽  
Vol 20 (8) ◽  
pp. 918-931
Author(s):  
Milad Ashrafizadeh ◽  
Reza Mohammadinejad ◽  
Saeed Samarghandian ◽  
Habib Yaribeygi ◽  
Thomas P. Johnston ◽  
...  
Keyword(s):  
Side Effects ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Malignant Cell ◽  
Malignant Cells ◽  
High Potency ◽  
Cancer Management ◽  
Naturally Occurring ◽  
Anti Cancer ◽  
Proliferation And Metastasis

Cancer management and/or treatment require a comprehensive understanding of the molecular and signaling pathways involved. Recently, much attention has been directed to these molecular and signaling pathways, and it has been suggested that a number of biomolecules/players involved in such pathways, such as PI3K/Akt, NF-κB, STAT, and Nrf2 contribute to the progression, invasion, proliferation, and metastasis of malignant cells. Synthetic anti-tumor agents and chemotherapeutic drugs have been a mainstay in cancer therapy and are widely used to suppress the progression and, hopefully, halt the proliferation of malignant cells. However, these agents have some undesirable side-effects and, therefore, naturally-occurring compounds with high potency and fewer side-effects are now of great interest. Osthole is a plant-derived chemical compound that can inhibit the proliferation of malignant cells and provide potent anti-cancer effects in various tissues. Therefore, in this review, we presented the main findings concerning the potential anti-tumor effects of osthole and its derivatives and described possible molecular mechanisms by which osthole may suppress malignant cell proliferation in different tissues.

scholarly journals Potential Antiviral Properties of Industrially Important Marine Algal Polysaccharides and Their Significance in Fighting a Future Viral Pandemic

Viruses ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1817
Author(s):  
Renu Geetha Bai ◽  
Rando Tuvikene
Keyword(s):  
Biomedical Applications ◽  
Marine Algae ◽  
Therapeutic Potential ◽  
Structural Diversity ◽  
Sulfated Polysaccharides ◽  
Inhibitory Effects ◽  
Marine Algal ◽  
Infection Processes ◽  
Algal Polysaccharides ◽  
Diverse Virus

Over the decades, the world has witnessed diverse virus associated pandemics. The significant inhibitory effects of marine sulfated polysaccharides against SARS-CoV-2 shows its therapeutic potential in future biomedical applications and drug development. Algal polysaccharides exhibited significant role in antimicrobial, antitumor, antioxidative, antiviral, anticoagulant, antihepatotoxic and immunomodulating activities. Owing to their health benefits, the sulfated polysaccharides from marine algae are a great deal of interest globally. Algal polysaccharides such as agar, alginate, carrageenans, porphyran, fucoidan, laminaran and ulvans are investigated for their nutraceutical potential at different stages of infection processes, structural diversity, complexity and mechanism of action. In this review, we focus on the recent antiviral studies of the marine algae-based polysaccharides and their potential towards antiviral medicines.

scholarly journals Caspase-Independent Regulated Necrosis Pathways as Potential Targets in Cancer Management

2021 ◽  
Vol 10 ◽  
Author(s):  
Jianyao Lou ◽  
Yunxiang Zhou ◽  
Zengyu Feng ◽  
Mindi Ma ◽  
Yihan Yao ◽  
...  
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Multiple Modes ◽  
Cancer Management ◽  
Regulated Necrosis ◽  
Anti Cancer ◽  
Cancer Initiation

Regulated necrosis is an emerging type of cell death independent of caspase. Recently, with increasing findings of regulated necrosis in the field of biochemistry and genetics, the underlying molecular mechanisms and signaling pathways of regulated necrosis are gradually understood. Nowadays, there are several modes of regulated necrosis that are tightly related to cancer initiation and development, including necroptosis, ferroptosis, parthanatos, pyroptosis, and so on. What’s more, accumulating evidence shows that various compounds can exhibit the anti-cancer effect via inducing regulated necrosis in cancer cells, which indicates that caspase-independent regulated necrosis pathways are potential targets in cancer management. In this review, we expand the molecular mechanisms as well as signaling pathways of multiple modes of regulated necrosis. We also elaborate on the roles they play in tumorigenesis and discuss how each of the regulated necrosis pathways could be therapeutically targeted.

scholarly journals Targets of Vitamin C With Therapeutic Potential for Cardiovascular Disease and Underlying Mechanisms: A Study of Network Pharmacology

2021 ◽  
Vol 11 ◽  
Author(s):  
Ning Zhu ◽  
Bingwu Huang ◽  
Wenbing Jiang
Keyword(s):  
Cardiovascular Disease ◽  
Vitamin C ◽  
Signaling Pathways ◽  
Therapeutic Potential ◽  
Interaction Network ◽  
Network Pharmacology ◽  
Therapeutic Effects ◽  
Biological Processes ◽  
Protective Effects ◽  
Bioinformatics Analyses

Vitamin C (ascorbic acid) is a nutrient used to treat cardiovascular disease (CVD). However, the pharmacological targets of vitamin C and the mechanisms underlying the therapeutic effects of vitamin C on CVD remain to be elucidated. In this study, we used network pharmacology approach to investigate the pharmacological mechanisms of vitamin C for the treatment of CVD. The core targets, major hubs, enriched biological processes, and key signaling pathways were identified. A protein-protein interaction network and an interaction diagram of core target-related pathways were constructed. Three core targets were identified, including phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform, signal transducer and activator of transcription-3 (STAT3), and prothrombin. The GO and KEGG analyses identified top 20 enriched biological processes and signaling pathways involved in the therapeutic effects of vitamin C on CVD. The JAK-STAT, STAT, PD1, EGFR, FoxO, and chemokines signaling pathways may be highly involved in the protective effects of vitamin C against CVD. In conclusion, our bioinformatics analyses provided evidence on the possible therapeutic mechanisms of vitamin C in CVD treatment, which may contribute to the development of novel drugs for CVD.

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