scholarly journals New Drugs from the Sea: Pro-Apoptotic Activity of Sponges and Algae Derived Compounds

Marine Drugs ◽  
2019 ◽  
Vol 17 (1) ◽  
pp. 31 ◽  
Author(s):  
Giuseppe Ercolano ◽  
Paola De Cicco ◽  
Angela Ianaro
Keyword(s):  
Molecular Mechanisms ◽  
Human Cancer ◽  
Biological Activities ◽  
Mitochondrial Pathway ◽  
Marine Organisms ◽  
New Drugs ◽  
Bioactive Molecules ◽  
Bioactive Metabolites ◽  
Apoptotic Activity

Natural compounds derived from marine organisms exhibit a wide variety of biological activities. Over the last decades, a great interest has been focused on the anti-tumour role of sponges and algae that constitute the major source of these bioactive metabolites. A substantial number of chemically different structures from different species have demonstrated inhibition of tumour growth and progression by inducing apoptosis in several types of human cancer. The molecular mechanisms by which marine natural products activate apoptosis mainly include (1) a dysregulation of the mitochondrial pathway; (2) the activation of caspases; and/or (3) increase of death signals through transmembrane death receptors. This great variety of mechanisms of action may help to overcome the multitude of resistances exhibited by different tumour specimens. Therefore, products from marine organisms and their synthetic derivates might represent promising sources for new anticancer drugs, both as single agents or as co-adjuvants with other chemotherapeutics. This review will focus on some selected bioactive molecules from sponges and algae with pro-apoptotic potential in tumour cells.

scholarly journals Marine Natural Products: A Source of Novel Anticancer Drugs

Marine Drugs ◽  
2019 ◽  
Vol 17 (9) ◽  
pp. 491 ◽  
Author(s):  
Shaden A. M. Khalifa ◽  
Nizar Elias ◽  
Mohamed A. Farag ◽  
Lei Chen ◽  
Aamer Saeed ◽  
...  
Keyword(s):  
Natural Products ◽  
Anticancer Drugs ◽  
Marine Natural Products ◽  
Molecular Mechanisms ◽  
Biological Effects ◽  
Marine Organisms ◽  
New Drugs ◽  
Bioactive Metabolites ◽  
Chemical Structures ◽  
The Impact

Cancer remains one of the most lethal diseases worldwide. There is an urgent need for new drugs with novel modes of action and thus considerable research has been conducted for new anticancer drugs from natural sources, especially plants, microbes and marine organisms. Marine populations represent reservoirs of novel bioactive metabolites with diverse groups of chemical structures. This review highlights the impact of marine organisms, with particular emphasis on marine plants, algae, bacteria, actinomycetes, fungi, sponges and soft corals. Anti-cancer effects of marine natural products in in vitro and in vivo studies were first introduced; their activity in the prevention of tumor formation and the related compound-induced apoptosis and cytotoxicities were tackled. The possible molecular mechanisms behind the biological effects are also presented. The review highlights the diversity of marine organisms, novel chemical structures, and chemical property space. Finally, therapeutic strategies and the present use of marine-derived components, its future direction and limitations are discussed.

scholarly journals Local anesthetics impair the growth and self-renewal of glioblastoma stem cells by inhibiting ZDHHC15-mediated GP130 palmitoylation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Xiaoqing Fan ◽  
Haoran Yang ◽  
Chenggang Zhao ◽  
Lizhu Hu ◽  
Delong Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Western Blot ◽  
Local Anesthetics ◽  
Molecular Mechanisms ◽  
Biological Activities ◽  
Xenograft Model ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Self Renewal

Abstract Background A large number of preclinical studies have shown that local anesthetics have a direct inhibitory effect on tumor biological activities, including cell survival, proliferation, migration, and invasion. There are few studies on the role of local anesthetics in cancer stem cells. This study aimed to determine the possible role of local anesthetics in glioblastoma stem cell (GSC) self-renewal and the underlying molecular mechanisms. Methods The effects of local anesthetics in GSCs were investigated through in vitro and in vivo assays (i.e., Cell Counting Kit 8, spheroidal formation assay, double immunofluorescence, western blot, and xenograft model). The acyl-biotin exchange method (ABE) assay was identified proteins that are S-acylated by zinc finger Asp-His-His-Cys-type palmitoyltransferase 15 (ZDHHC15). Western blot, co-immunoprecipitation, and liquid chromatograph mass spectrometer-mass spectrometry assays were used to explore the mechanisms of ZDHHC15 in effects of local anesthetics in GSCs. Results In this study, we identified a novel mechanism through which local anesthetics can damage the malignant phenotype of glioma. We found that local anesthetics prilocaine, lidocaine, procaine, and ropivacaine can impair the survival and self-renewal of GSCs, especially the classic glioblastoma subtype. These findings suggest that local anesthetics may weaken ZDHHC15 transcripts and decrease GP130 palmitoylation levels and membrane localization, thus inhibiting the activation of IL-6/STAT3 signaling. Conclusions In conclusion, our work emphasizes that ZDHHC15 is a candidate therapeutic target, and local anesthetics are potential therapeutic options for glioblastoma.

scholarly journals Hunting Bioactive Molecules from the Agave Genus: An Update on Extraction and Biological Potential

Molecules ◽  
2021 ◽  
Vol 26 (22) ◽  
pp. 6789
Author(s):  
Misael Bermúdez-Bazán ◽  
Gustavo Adolfo Castillo-Herrera ◽  
Judith Esmeralda Urias-Silvas ◽  
Antonio Escobedo-Reyes ◽  
Mirna Estarrón-Espinosa
Keyword(s):  
Secondary Metabolites ◽  
Biological Activities ◽  
Waste Product ◽  
Bioactive Molecules ◽  
Alcoholic Beverages ◽  
Therapeutic Benefits ◽  
Biological Potential ◽  
Novel Drugs ◽  
Ancient Times

Agaves are plants used in the production of alcoholic beverages and fibers. Ever since ancient times, pre-Hispanic cultures in Mexico have used them in traditional medicine to cure different ailments. Over the years, studies of the active principles responsible for the therapeutic benefits of agaves have increased. Leaves and fibers are the main agro-wastes generated in tequila and mezcal production, while fibers are the main waste product in the textile sector. Different investigations have referred to the agro-waste from agave processing as a source of bioactive molecules called secondary metabolites (SM). Among them, phenols, flavonoids, phytosterols, and saponins have been extracted, identified, and isolated from these plants. The role of these molecules in pest control and the prospect of metabolites with the biological potential to develop novel drugs for chronic and acute diseases represent new opportunities to add value to these agro-wastes. This review aims to update the biological activities and recent applications of the secondary metabolites of the genus Agave.

scholarly journals The role of drugs in the control of parasitic nematode infections: must we do without?

Parasitology ◽  
1997 ◽  
Vol 114 (7) ◽  
pp. 137-144 ◽  
Author(s):  
M. H. ROOS
Keyword(s):  
Broad Spectrum ◽  
Molecular Mechanisms ◽  
Parasite Species ◽  
Parasitic Nematode ◽  
New Drugs ◽  
Pharmaceutical Companies ◽  
Parasitic Helminths ◽  
Parasite Populations ◽  
Drug Resistant Parasite

Parasitic helminths (worms) cause serious infectious diseases in humans and domestic animals. Control of these infections relies mostly on chemotherapeutics (the anthelmintics), but resistance has developed against most of these broad-spectrum drugs in many parasite species. These resistant parasites are being used to elucidate the molecular mechanisms of drug resistance and drug action. This has led to the development of sensitive assays to detect resistant parasites, but this has not delayed the emergence of additional drug resistant parasite populations. Therefore, as development of new drugs by pharmaceutical companies is slow, we may have to be prepared for a time when broad-spectrum drugs are no longer effective, especially against worms of sheep.

Marine Genetic Resources. A Source of New Drugs The Experience of the Biotechnology Sector

2009 ◽  
Vol 24 (2) ◽  
pp. 209-220 ◽  
Author(s):  
Fernando de la Calle
Keyword(s):  
Drug Discovery ◽  
Genetic Resources ◽  
Dna Analysis ◽  
Marine Organisms ◽  
New Drugs ◽  
Bioactive Molecules ◽  
Scale Production ◽  
Discovery Process ◽  
Drug Discovery Process ◽  
The Status

AbstractThis article provides an overview of the conversion of marine genetic resources into new drugs. Three marine organisms suitable for application in human health and steps in the drug discovery process are described. Specific supply problems resulting from the minute concentration of required compounds for medicine in the natural marine source are examined. Three case studies illustrate different strategies enabling an industrial-scale production: chemical synthesis, biotechnology and fermentation. Future concepts for marine scientific research which could lead to new medical applications are considered. Besides research in unexplored deep sea areas, the “metagenomic approach” particularly might lead to significant new achievements. This DNA analysis of marine organisms facilitates the drug discovery process because it requires significantly less marine material than current approaches. Because this process, starting with the search for bioactive molecules and continuing with the production of drug-like molecules before finally reaching the status of medicine, can take up to 20 years, the development of medicine is a very long and risky venture.

scholarly journals Role of Endoplasmic Reticulum Stress in the Anticancer Activity of Natural Compounds

2019 ◽  
Vol 20 (4) ◽  
pp. 961 ◽  
Author(s):  
Patrizia Limonta ◽  
Roberta Moretti ◽  
Monica Marzagalli ◽  
Fabrizio Fontana ◽  
Michela Raimondi ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Anticancer Activity ◽  
Molecular Mechanisms ◽  
Natural Compounds ◽  
New Drugs ◽  
Bioactive Molecules ◽  
Green Tea Polyphenols ◽  
Cell Death Pathways ◽  
Incidence And Mortality

Cancer represents a serious global health problem, and its incidence and mortality are rapidly growing worldwide. One of the main causes of the failure of an anticancer treatment is the development of drug resistance by cancer cells. Therefore, it is necessary to develop new drugs characterized by better pharmacological and toxicological profiles. Natural compounds can represent an optimal collection of bioactive molecules. Many natural compounds have been proven to possess anticancer effects in different types of tumors, but often the molecular mechanisms associated with their cytotoxicity are not completely understood. The endoplasmic reticulum (ER) is an organelle involved in multiple cellular processes. Alteration of ER homeostasis and its appropriate functioning originates a cascade of signaling events known as ER stress response or unfolded protein response (UPR). The UPR pathways involve three different sensors (protein kinase RNA(PKR)-like ER kinase (PERK), inositol requiring enzyme1α (IRE1) and activating transcription factor 6 (ATF6)) residing on the ER membranes. Although the main purpose of UPR is to restore this organelle’s homeostasis, a persistent UPR can trigger cell death pathways such as apoptosis. There is a growing body of evidence showing that ER stress may play a role in the cytotoxicity of many natural compounds. In this review we present an overview of different plant-derived natural compounds, such as curcumin, resveratrol, green tea polyphenols, tocotrienols, and garcinia derivates, that exert their anticancer activity via ER stress modulation in different human cancers.

scholarly journals Bcl-2 Family Proteins in Development and Treatment of Malignant Diseases

2011 ◽  
Vol 11 (3) ◽  
pp. 15-23 ◽  
Author(s):  
P. Racay ◽  
J. Jurecekova ◽  
A. Stefanikova ◽  
K. Klikova ◽  
J. Hatok ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Cell Biology ◽  
Molecular Mechanisms ◽  
Cell Signalling ◽  
Acquired Resistance ◽  
Therapy Response ◽  
Mitochondrial Pathway ◽  
New Drugs ◽  
Malignant Cells ◽  
Malignant Diseases

Bcl-2 Family Proteins in Development and Treatment of Malignant DiseasesProteins of Bcl-2 family are key regulators of mitochondrial pathway of apoptosis. Deregulation of apoptosis disrupts the complex and delicate balance between cell proliferation, survival and death and plays an important role in the development of malignant diseases. In addition to uncontrolled proliferation, alterations in apoptotic proteins are frequently associated with resistance of malignant cells to chemotherapy, leading to ineffective treatment with chemotherapy that primarily acts by apoptosis initiation. Despite the progress in combinatory and biologic therapy, response rates for treatment of different malignant diseases are not high enough. Therefore, new anti-cancer agents that selectively kill tumour cells and spare normal tissues are still urgently needed. Progress in biochemistry and cell biology leading to detailed dissection of cell signalling pathways allows development of new therapeutic strategies targeting different proteins involved in malignant transformation and uncontrolled proliferation of malignant cells. Emerging knowledge on molecular mechanisms of apoptosis deregulation in cancer development has revealed Bcl-2 family proteins as potential targets for drugs discovery. Structural analysis of these proteins together with studies of apoptosis mechanisms have outlined strategies for generation of new drugs, resulting in numerous novel chemical entities with mechanism-based activity. Many of the most logical targets for promoting apoptosis of malignant cells are technically challenging, involving often disruption of protein interactions or changes in gene expression, as opposed to traditional pharmaceutical approach that predominantly attacks enzymes. Understanding of the core components of the apoptotic machinery at the molecular and structural levels may lead to new era in cancer therapy where the intrinsic and acquired resistance of malignant cells to apoptosis can be pharmacologically reversed, reinstating natural pathways of cell suicide.

scholarly journals BIOLOGICAL ACTIVITIES OF ALTERNARIA SP. RL4 – A POTENT ENDOPHYTIC FUNGUS ASSOCIATED WITH RAUVOLFIA SERPENTINA L. BENTH.

2018 ◽  
Vol 11 (11) ◽  
pp. 178
Author(s):  
Ranjan Ghosh ◽  
Soma Barman ◽  
Pavan Kumar Jgs ◽  
Narayan C Mandal
Keyword(s):  
Mode Of Action ◽  
Pathogenic Bacteria ◽  
Biological Activities ◽  
Fungal Endophytes ◽  
Radical Scavenging ◽  
New Drugs ◽  
Bioactive Metabolites ◽  
Gram Positive ◽  
Rauvolfia Serpentina ◽  
Alternaria Sp

Objectives: Endophytic fungi are considered as an important source of bioactive metabolites. The present study focused on the isolation of potent endophytic fungal strains from well-known medicinal plant Rauvolfia serpentina L. Benth. having biological activities.Materials & Methods: Fungal endophytes were isolated from aerial parts of the plant and the potent strain was selected on the basis of antibacterial activities of cell-free supernatant (CFS). Ethyl acetate (EA) extraction of CFS was done and mode of action of EA fraction was checked against pathogenic bacteria. EA fraction was also analyzed by thin-layer chromatography (TLC). In addition, antioxidant activity was checked by 1,1-Diphenyl- 2-picrylhydrazyl-free radical scavenging assay and anticancer activity was checked against breast cancer cell line MCF-7 by MTT assay.Results: Among the different endophytic fungal isolates, CFS of Alternaria sp. RL4 produced prominent zones of inhibition against numbers of Gram-positive pathogenic bacteria including Staphylococcus aureus (12±0.5 mm) and Listeria monocytogenes (17±2.0 mm). Massive reductions in bacterial CFS were noticed upon treatment with EA fraction (2 mg/ml). It also showed strong cidal mode of action against Gram-positive organisms. TLC analysis revealed the production of two different compounds with antibacterial potentials. In addition, EA fraction of RL4 showed very good antioxidant property with an IC50 value of 49.80±2.11μg/ml. MTT assay also suggested the anticancerous properties of EA fraction of RL4.Conclusion: Alternaria sp. RL4 could be a very good source of bioactive compounds for the development of new drugs.

scholarly journals A chemophenetic study of the genus Maytenus s.l. (Celastraceae): contribution to the rational search of its bioactive metabolites

Rodriguésia ◽  
2020 ◽  
Vol 71 ◽  
Author(s):  
Lorena Diniz Guimarães ◽  
Fernanda Moreira do Amaral ◽  
Natalia Barros dos Santos ◽  
Ana Joffily ◽  
Maria Carolina Anholeti ◽  
...  
Keyword(s):  
Biological Activities ◽  
New Drugs ◽  
Quinone Methide ◽  
Bioactive Metabolites ◽  
Quinone Methides ◽  
Multiple Functions ◽  
Structural Variety ◽  
Plant Groups ◽  
Antitumor Potential ◽  
Chemosystematic Markers

Abstract Maytenus s.l. is a genus of the Celastraceae family and many of its species are used in traditional medicine. Most of the substances responsible for the biological activities of plants come from their secondary metabolism, such as terpenoids and flavonoids, which have multiple functions in the plant and can occur in a similar way in plant groups. Chemophenetics analyzes the occurrence of these substances in a taxon and can infer evolutionary trends and contribute to the rational search for new drugs. Chemosystematic parameters were used to analyze the data obtained through a bibliographic survey. The species of Maytenus s.l. were separated into three groups: species with accepted names, synonymous species with the genus Monteverdia and synonymous species with the genus Gymnosporia. Due to their great occurrence and structural variety in Maytenus s.l., triterpenes were chosen as chemosystematic markers, with friedelanes and quinone methide triterpenes being the most expressive types. Studies have already demonstrated the analgesic potential of quinone methides and the antitumor potential of phenolic triterpenes and dimers of these units. Together, the three classes assist in the circumscription of Maytenus s.s. and Monteverdia, while lupanes can be used in the separation of these genera. Oleanans are representative of Gymnosporia.

scholarly journals piRNAs and PIWI proteins as potential biomarkers in ‌Breast cancer

2021 ◽  
Author(s):  
MANDANA Amelimojarad ◽  
Melika Amelimojarad
Keyword(s):  
Breast Cancer ◽  
Therapeutic Strategy ◽  
Molecular Mechanisms ◽  
Biological Activities ◽  
Diagnostic Biomarker ◽  
Gene And Protein Expression ◽  
Different Types ◽  
Non Coding Rnas ◽  
Generation Sequencing

Abstract PIWI-interacting RNAs (piRNAs) are another subgroup of small non-coding RNAs, that can play different biological activities further to their capabilities in the germline such as regulating the gene and protein expression, epigenetic silencing of transposable elements, and regulating the spermatogenesis by interacting with PIWI proteins. Recently, with the help of next-generation sequencing, abnormal expression of piRNAs have been observed in different types of cancer such as breast cancer (BC). A new investigation proposes piRNA as a prognostic and diagnostic biomarker in the treatment of BC. Therefore, this review aims to focus on the role of piRNAs in the initiation, progression, and metastasis of BC and its molecular mechanisms to understand its function and provide a better therapeutic strategy.

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