scholarly journals Saponin-Rich Extracts and Their Acid Hydrolysates Differentially Target Colorectal Cancer Metabolism in the Frame of Precision Nutrition

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3399
Author(s):  
Marta Gómez de Cedrón ◽  
Joaquín Navarro del Hierro ◽  
Marina Reguero ◽  
Sonia Wagner ◽  
Adrián Bouzas ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lipid Metabolism ◽  
Molecular Mechanisms ◽  
Cancer Metabolism ◽  
Therapeutic Potential ◽  
Biological Activities ◽  
Aerobic Glycolysis ◽  
Metabolic Reprogramming ◽  
Specific Subgroup ◽  
Bioactive Agents

Saponins or their aglycone form, sapogenin, have recently gained interest as bioactive agents due to their biological activities, their antitumoral effects being among them. Metabolic reprogramming has been recognized as a hallmark of cancer and, together with the increased aerobic glycolysis and glutaminolysis, the altered lipid metabolism is considered crucial to support cancer initiation and progression. The purpose of this study was to assess and compare the inhibitory effects on colorectal cancer cell lines of saponin-rich extracts from fenugreek and quinoa (FE and QE, respectively) and their hydrolyzed extracts as sapogenin-rich extracts (HFE and HQE, respectively). By mean of the latest technology in the analysis of cell bioenergetics, we demonstrate that FE and HFE diminished mitochondrial oxidative phosphorylation and aerobic glycolysis; meanwhile, quinoa extracts did not show relevant activities. Distinct molecular mechanisms were identified for fenugreek: FE inhibited the expression of TYMS1 and TK1, synergizing with the chemotherapeutic drug 5-fluorouracil (5-FU); meanwhile, HFE inhibited lipid metabolism targets, leading to diminished intracellular lipid content. The relevance of considering the coexisting compounds of the extracts or their hydrolysis transformation as innovative strategies to augment the therapeutic potential of the extracts, and the specific subgroup of patients where each extract would be more beneficial, are discussed in the frame of precision nutrition.

scholarly journals Hemistepsin A suppresses colorectal cancer growth through inhibiting pyruvate dehydrogenase kinase activity

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ling Jin ◽  
Eun-Yeong Kim ◽  
Tae-Wook Chung ◽  
Chang Woo Han ◽  
So Young Park ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Cells ◽  
Pyruvate Dehydrogenase ◽  
Cancer Metabolism ◽  
Aerobic Glycolysis ◽  
Lactate Production ◽  
Pyruvate Dehydrogenase Kinase ◽  
Cancer Drug ◽  
Potential Candidate ◽  
Mitochondrial Ros

AbstractMost cancer cells primarily produce their energy through a high rate of glycolysis followed by lactic acid fermentation even in the presence of abundant oxygen. Pyruvate dehydrogenase kinase (PDK) 1, an enzyme responsible for aerobic glycolysis via phosphorylating and inactivating pyruvate dehydrogenase (PDH) complex, is commonly overexpressed in tumors and recognized as a therapeutic target in colorectal cancer. Hemistepsin A (HsA) is a sesquiterpene lactone isolated from Hemistepta lyrata Bunge (Compositae). Here, we report that HsA is a PDK1 inhibitor can reduce the growth of colorectal cancer and consequent activation of mitochondrial ROS-dependent apoptotic pathway both in vivo and in vitro. Computational simulation and biochemical assays showed that HsA directly binds to the lipoamide-binding site of PDK1, and subsequently inhibits the interaction of PDK1 with the E2 subunit of PDH complex. As a result of PDK1 inhibition, lactate production was decreased, but oxygen consumption was increased. Mitochondrial ROS levels and mitochondrial damage were also increased. Consistent with these observations, the apoptosis of colorectal cancer cells was promoted by HsA with enhanced activation of caspase-3 and -9. These results suggested that HsA might be a potential candidate for developing a novel anti-cancer drug through suppressing cancer metabolism.

scholarly journals Metabolic Anti-Cancer Effects of Melatonin: Clinically Relevant Prospects

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 3018
Author(s):  
Marek Samec ◽  
Alena Liskova ◽  
Lenka Koklesova ◽  
Kevin Zhai ◽  
Elizabeth Varghese ◽  
...  
Keyword(s):  
Cancer Metabolism ◽  
Glucose Transporter ◽  
Aerobic Glycolysis ◽  
Cell Metabolism ◽  
Lactate Production ◽  
Pentose Phosphate ◽  
Metabolic Reprogramming ◽  
Effective Prevention ◽  
Anti Cancer ◽  
Glucose 6 Phosphate Dehydrogenase

Metabolic reprogramming characterized by alterations in nutrient uptake and critical molecular pathways associated with cancer cell metabolism represents a fundamental process of malignant transformation. Melatonin (N-acetyl-5-methoxytryptamine) is a hormone secreted by the pineal gland. Melatonin primarily regulates circadian rhythms but also exerts anti-inflammatory, anti-depressant, antioxidant and anti-tumor activities. Concerning cancer metabolism, melatonin displays significant anticancer effects via the regulation of key components of aerobic glycolysis, gluconeogenesis, the pentose phosphate pathway (PPP) and lipid metabolism. Melatonin treatment affects glucose transporter (GLUT) expression, glucose-6-phosphate dehydrogenase (G6PDH) activity, lactate production and other metabolic contributors. Moreover, melatonin modulates critical players in cancer development, such as HIF-1 and p53. Taken together, melatonin has notable anti-cancer effects at malignancy initiation, progression and metastasing. Further investigations of melatonin impacts relevant for cancer metabolism are expected to create innovative approaches supportive for the effective prevention and targeted therapy of cancers.

scholarly journals Epithelial–Mesenchymal Transition (EMT) Induced by TGF-β in Hepatocellular Carcinoma Cells Reprograms Lipid Metabolism

2021 ◽  
Vol 22 (11) ◽  
pp. 5543
Author(s):  
Jitka Soukupova ◽  
Andrea Malfettone ◽  
Esther Bertran ◽  
María Isabel Hernández-Alvarez ◽  
Irene Peñuelas-Haro ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Lipid Metabolism ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Aerobic Glycolysis ◽  
Metabolic Reprogramming ◽  
Migration And Invasion ◽  
Metabolic Switch ◽  
Mesenchymal Transition ◽  
Hcc Cells

(1) Background: The transforming growth factor (TGF)-β plays a dual role in liver carcinogenesis. At early stages, it inhibits cell growth and induces apoptosis. However, TGF-β expression is high in advanced stages of hepatocellular carcinoma (HCC) and cells become resistant to TGF-β induced suppressor effects, responding to this cytokine undergoing epithelial–mesenchymal transition (EMT), which contributes to cell migration and invasion. Metabolic reprogramming has been established as a key hallmark of cancer. However, to consider metabolism as a therapeutic target in HCC, it is necessary to obtain a better understanding of how reprogramming occurs, which are the factors that regulate it, and how to identify the situation in a patient. Accordingly, in this work we aimed to analyze whether a process of full EMT induced by TGF-β in HCC cells induces metabolic reprogramming. (2) Methods: In vitro analysis in HCC cell lines, metabolomics and transcriptomics. (3) Results: Our findings indicate a differential metabolic switch in response to TGF-β when the HCC cells undergo a full EMT, which would favor lipolysis, increased transport and utilization of free fatty acids (FFA), decreased aerobic glycolysis and an increase in mitochondrial oxidative metabolism. (4) Conclusions: EMT induced by TGF-β in HCC cells reprograms lipid metabolism to facilitate the utilization of FFA and the entry of acetyl-CoA into the TCA cycle, to sustain the elevated requirements of energy linked to this process.

scholarly journals Regulation of Osteoclast Differentiation and Activity by Lipid Metabolism

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 89
Author(s):  
Haemin Kim ◽  
Brian Oh ◽  
Kyung-Hyun Park-Min
Keyword(s):  
Lipid Metabolism ◽  
Molecular Mechanisms ◽  
Bone Cells ◽  
Critical Role ◽  
Osteoclast Differentiation ◽  
Bone Diseases ◽  
Metabolic Reprogramming ◽  
Lipid Lowering ◽  
Metabolic Bone Diseases ◽  
Increased Risk

Bone is a dynamic tissue and is constantly being remodeled by bone cells. Metabolic reprogramming plays a critical role in the activation of these bone cells and skeletal metabolism, which fulfills the energy demand for bone remodeling. Among various metabolic pathways, the importance of lipid metabolism in bone cells has long been appreciated. More recent studies also establish the link between bone loss and lipid-altering conditions—such as atherosclerotic vascular disease, hyperlipidemia, and obesity—and uncover the detrimental effect of fat accumulation on skeletal homeostasis and increased risk of fracture. Targeting lipid metabolism with statin, a lipid-lowering drug, has been shown to improve bone density and quality in metabolic bone diseases. However, the molecular mechanisms of lipid-mediated regulation in osteoclasts are not completely understood. Thus, a better understanding of lipid metabolism in osteoclasts can be used to harness bone cell activity to treat pathological bone disorders. This review summarizes the recent developments of the contribution of lipid metabolism to the function and phenotype of osteoclasts.

scholarly journals Mitochondrial Metabolism in PDAC: From Better Knowledge to New Targeting Strategies

Biomedicines ◽  
2020 ◽  
Vol 8 (8) ◽  
pp. 270 ◽  
Author(s):  
Gabriela Reyes-Castellanos ◽  
Rawand Masoud ◽  
Alice Carrier
Keyword(s):  
Cancer Therapy ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Cancer Metabolism ◽  
Aerobic Glycolysis ◽  
Mitochondrial Metabolism ◽  
Metabolic Reprogramming ◽  
Ductal Adenocarcinoma ◽  
Current View ◽  
Pancreatic Cancer Cells

Cancer cells reprogram their metabolism to meet bioenergetics and biosynthetic demands. The first observation of metabolic reprogramming in cancer cells was made a century ago (“Warburg effect” or aerobic glycolysis), leading to the classical view that cancer metabolism relies on a glycolytic phenotype. There is now accumulating evidence that most cancers also rely on mitochondria to satisfy their metabolic needs. Indeed, the current view of cancer metabolism places mitochondria as key actors in all facets of cancer progression. Importantly, mitochondrial metabolism has become a very promising target in cancer therapy, including for refractory cancers such as Pancreatic Ductal AdenoCarcinoma (PDAC). In particular, mitochondrial oxidative phosphorylation (OXPHOS) is an important target in cancer therapy. Other therapeutic strategies include the targeting of glutamine and fatty acids metabolism, as well as the inhibition of the TriCarboxylic Acid (TCA) cycle intermediates. A better knowledge of how pancreatic cancer cells regulate mitochondrial metabolism will allow the identification of metabolic vulnerabilities and thus novel and more efficient therapeutic options for the benefit of each patient.

Clinical Applications of Antimicrobial Peptides (AMPs): Where do we Stand Now?

2020 ◽  
Vol 27 (2) ◽  
pp. 120-134 ◽  
Author(s):  
Mithoor Divyashree ◽  
Madhu K. Mani ◽  
Dhanasekhar Reddy ◽  
Ranjith Kumavath ◽  
Preetam Ghosh ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Therapeutic Potential ◽  
Biological Activities ◽  
Wide Spectrum ◽  
Noncommunicable Diseases ◽  
Multi Drug Resistance ◽  
Food Preservatives ◽  
Pharmaceutical Industries

: In this era of multi-drug resistance (MDR), antimicrobial peptides (AMPs) are one of the most promising classes of potential drug candidates to combat communicable as well as noncommunicable diseases such as cancers and diabetes. AMPs show a wide spectrum of biological activities which include antiviral, antifungal, anti-mitogenic, anticancer, and anti-inflammatory properties. Apart from these prospective therapeutic potentials, the AMPs can act as food preservatives and immune modulators. Therefore, AMPs have the potential to replace conventional drugs and may gain a significant global drug market share. Although several AMPs have shown therapeutic potential in vitro or in vivo, in most cases they have failed the clinical trial owing to various issues. In this review, we discuss in brief (i) molecular mechanisms of AMPs in various diseases, (ii) importance of AMPs in pharmaceutical industries, (iii) the challenges in using AMPs as therapeutics and how to overcome, (iv) available AMP therapeutics in market, and (v) AMPs under clinical trials. Here, we specifically focus on the therapeutic AMPs in the areas of dermatology, surgery, oncology and metabolic diseases.

scholarly journals The role of ubiquitination and deubiquitination in cancer metabolism

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Tianshui Sun ◽  
Zhuonan Liu ◽  
Qing Yang
Keyword(s):  
Cancer Metabolism ◽  
Biological Activities ◽  
Redox Homeostasis ◽  
Metabolic Reprogramming ◽  
Post Translational Modification ◽  
Cancer Cell Growth ◽  
Post Translational Modifications ◽  
New Therapeutic Approaches ◽  
Complex Process

Abstract Metabolic reprogramming, including enhanced biosynthesis of macromolecules, altered energy metabolism, and maintenance of redox homeostasis, is considered a hallmark of cancer, sustaining cancer cell growth. Multiple signaling pathways, transcription factors and metabolic enzymes participate in the modulation of cancer metabolism and thus, metabolic reprogramming is a highly complex process. Recent studies have observed that ubiquitination and deubiquitination are involved in the regulation of metabolic reprogramming in cancer cells. As one of the most important type of post-translational modifications, ubiquitination is a multistep enzymatic process, involved in diverse cellular biological activities. Dysregulation of ubiquitination and deubiquitination contributes to various disease, including cancer. Here, we discuss the role of ubiquitination and deubiquitination in the regulation of cancer metabolism, which is aimed at highlighting the importance of this post-translational modification in metabolic reprogramming and supporting the development of new therapeutic approaches for cancer treatment.

scholarly journals Induction of ferroptosis in human nasopharyngeal cancer cells by cucurbitacin B: molecular mechanism and therapeutic potential

2021 ◽  
Vol 12 (3) ◽  
Author(s):  
Shuai Huang ◽  
Bihui Cao ◽  
Jinling Zhang ◽  
Yunfei Feng ◽  
Lu Wang ◽  
...  
Keyword(s):  
Molecular Mechanism ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Tumour Progression ◽  
Biological Activities ◽  
Nasopharyngeal Cancer ◽  
Migration And Invasion ◽  
Cucurbitacin B

AbstractCucurbitacin B (CuB) is a widely available triterpenoid molecule that exhibits various biological activities. Previous studies on the anti-tumour mechanism of CuB have mostly focused on cell apoptosis, and research on the ferroptosis-inducing effect has rarely been reported. Herein, we first discovered the excellent cytotoxicity of CuB towards human nasopharyngeal carcinoma cells and elucidated its potential ferroptosis-inducing mechanisms. Morphology alterations of mitochondrial ultrastructure, as observed via transmission electron microscopy, showed that CuB-treated cells undergo ferroptosis. CuB caused intracellular accumulation of iron ions and depletion of glutathione. Detailed molecular mechanism investigation confirmed that CuB both induced widespread lipid peroxidation and downregulated the expression of GPX4, ultimately initiating a multipronged mechanism of ferroptosis. Furthermore, CuB exhibited anti-tumour effects in vitro by inhibiting cellular microtubule polymerization, arresting cell cycle and suppressing migration and invasion. Finally, CuB significantly inhibited tumour progression without causing obvious side effects in vivo. Altogether, our study highlighted the therapeutic potential of CuB as a ferroptosis-inducing agent for nasopharyngeal cancer, and it provided valuable insights for developing effective anti-tumour agents with novel molecular mechanisms derived from natural products.

scholarly journals Advances in the study of emodin: an update on pharmacological properties and mechanistic basis

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Qi Zheng ◽  
Shuo Li ◽  
Xiaojiaoyang Li ◽  
Runping Liu
Keyword(s):  
Targeted Delivery ◽  
Pathogenic Bacteria ◽  
Molecular Mechanisms ◽  
Viral Infections ◽  
Therapeutic Potential ◽  
Biological Activities ◽  
Molecular Targets ◽  
Virus Infections ◽  
Recent Developments ◽  
Mechanistic Basis

AbstractRhei Radix et Rhizoma, also known as rhubarb or Da Huang, has been widely used as a spice and as traditional herbal medicine for centuries, and is currently marketed in China as the principal herbs in various prescriptions, such as Da-Huang-Zhe-Chong pills and Da-Huang-Qing-Wei pills. Emodin, a major bioactive anthraquinone derivative extracted from rhubarb, represents multiple health benefits in the treatment of a host of diseases, such as immune-inflammatory abnormality, tumor progression, bacterial or viral infections, and metabolic syndrome. Emerging evidence has made great strides in clarifying the multi-targeting therapeutic mechanisms underlying the efficacious therapeutic potential of emodin, including anti-inflammatory, immunomodulatory, anti-fibrosis, anti-tumor, anti-viral, anti-bacterial, and anti-diabetic properties. This comprehensive review aims to provide an updated summary of recent developments on these pharmacological efficacies and molecular mechanisms of emodin, with a focus on the underlying molecular targets and signaling networks. We also reviewed recent attempts to improve the pharmacokinetic properties and biological activities of emodin by structural modification and novel material-based targeted delivery. In conclusion, emodin still has great potential to become promising therapeutic options to immune and inflammation abnormality, organ fibrosis, common malignancy, pathogenic bacteria or virus infections, and endocrine disease or disorder. Scientifically addressing concerns regarding the poor bioavailability and vague molecular targets would significantly contribute to the widespread acceptance of rhubarb not only as a dietary supplement in food flavorings and colorings but also as a health-promoting TCM in the coming years.

scholarly journals Cancer metabolism and intervention therapy

2021 ◽  
Vol 2 (1) ◽  
Author(s):  
Huakan Zhao ◽  
Yongsheng Li
Keyword(s):  
Cancer Cells ◽  
Tumor Cells ◽  
Cancer Metabolism ◽  
Aerobic Glycolysis ◽  
Acid Synthesis ◽  
Pentose Phosphate ◽  
Metabolic Reprogramming ◽  
Cancer Therapies ◽  
Proliferation And Metastasis ◽  
Immunosuppressive Microenvironment

AbstractMetabolic reprogramming with heterogeneity is a hallmark of cancer and is at the basis of malignant behaviors. It supports the proliferation and metastasis of tumor cells according to the low nutrition and hypoxic microenvironment. Tumor cells frantically grab energy sources (such as glucose, fatty acids, and glutamine) from different pathways to produce a variety of biomass to meet their material needs via enhanced synthetic pathways, including aerobic glycolysis, glutaminolysis, fatty acid synthesis (FAS), and pentose phosphate pathway (PPP). To survive from stress conditions (e.g., metastasis, irradiation, or chemotherapy), tumor cells have to reprogram their metabolism from biomass production towards the generation of abundant adenosine triphosphate (ATP) and antioxidants. In addition, cancer cells remodel the microenvironment through metabolites, promoting an immunosuppressive microenvironment. Herein, we discuss how the metabolism is reprogrammed in cancer cells and how the tumor microenvironment is educated via the metabolic products. We also highlight potential metabolic targets for cancer therapies.

Sign in / Sign up

Export Citation Format

Share Document