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1.
Marine biomass diversity is a tremendous source of potential anticancer compounds. Several natural marine products have been described to restore tumor cell sensitivity to TNF-related apoptosis inducing ligand (TRAIL)-induced cell death. TRAIL is involved during tumor immune surveillance. Its selectivity for cancer cells has attracted much attention in oncology. This review aims at discussing the main mechanisms by which TRAIL signaling is regulated and presenting how marine bioactive compounds have been found, so far, to overcome TRAIL resistance in tumor cells. 相似文献
2.
Carmela Gallo Giusi Barra Marisa Saponaro Emiliano Manzo Laura Fioretto Marcello Ziaco Genoveffa Nuzzo Giuliana d&#x;Ippolito Raffaele De Palma Angelo Fontana 《Marine drugs》2020,18(12)
Immunotherapy takes advantage of the immune system to prevent, control, and eliminate neoplastic cells. The research in the field has already led to major breakthroughs to treat cancer. In this work, we describe a platform that integrates in vitro bioassays to test the immune response and direct antitumor effects for the preclinical discovery of anticancer candidates. The platform relies on the use of dendritic cells that are professional antigen-presenting cells (APC) able to activate T cells and trigger a primary adaptive immune response. The experimental procedure is based on two phenotypic assays for the selection of chemical leads by both a panel of nine tumor cell lines and growth factor-dependent immature mouse dendritic cells (D1). The positive hits are then validated by a secondary test on human monocyte-derived dendritic cells (MoDCs). The aim of this approach is the selection of potential immunotherapeutic small molecules from natural extracts or chemical libraries. 相似文献
3.
Jong-Young Kwak 《Marine drugs》2014,12(2):851-870
Fucoidan is a fucose-containing sulfated polysaccharide derived from brown seaweeds, crude extracts of which are commercially available as nutritional supplements. Recent studies have demonstrated antiproliferative, antiangiogenic, and anticancer properties of fucoidan in vitro. Accordingly, the anticancer effects of fucoidan have been shown to vary depending on its structure, while it can target multiple receptors or signaling molecules in various cell types, including tumor cells and immune cells. Low toxicity and the in vitro effects of fucoidan mentioned above make it a suitable agent for cancer prevention or treatment. However, preclinical development of natural marine products requires in vivo examination of purified compounds in animal tumor models. This review discusses the effects of systemic and local administration of fucoidan on tumor growth, angiogenesis, and immune reaction and whether in vivo and in vitro results are likely applicable to the development of fucoidan as a marine anticancer drug. 相似文献
4.
Cancer has always been a threat to human health with its high morbidity and mortality rates. Traditional therapy, including surgery, chemotherapy and radiotherapy, plays a key role in cancer treatment. However, it is not able to prevent tumor recurrence, drug resistance and treatment side effects, which makes it a very attractive challenge to search for new effective and specific anticancer drugs. Nature is a valuable source of multiple pharmaceuticals, and most of the anticancer drugs are natural products or derived from them. Marine-derived compounds, such as nucleotides, proteins, peptides and amides, have also shed light on cancer therapy, and they are receiving a fast-growing interest due to their bioactive properties. Their mechanisms contain anti-angiogenic, anti-proliferative and anti-metastasis activities; cell cycle arrest; and induction of apoptosis. This review provides an overview on the development of marine-derived compounds with anticancer properties, both their applications and mechanisms, and discovered technologies. 相似文献
5.
Plant natural products including alkaloids,polyphenols,terpenoids and flavonoids have been reported to exert anticancer activity by targeting various metabolic pathways.The biological pathways regulated by plant products can serve as novel drug targets.Plant natural compounds or their derivatives used for cancer treatment and some novel plant-based compounds which are used in clinical trials were discussed.Callus suspension culture with secondary metabolites can provide a continuous source of plant pharmaceuticals without time and space limitations.Previous research has shown that rice callus suspension culture can kill>95%cancer cells with no significant effect on the growth of normal cells.The role of candidate genes and metabolites which are likely to be involved in the process and their potential to serve as anticancer and anti-inflammatory agents were discussed.Large scale production of plant callus suspension culture and its constituents can be achieved using elicitors which enhance specific secondary metabolites combined with bioprocess technology. 相似文献
6.
Breast cancer resistance protein (BCRP) is a protein belonging to the ATP-binding cassette (ABC) transporter superfamily that has clinical relevance due to its multi-drug resistance properties in cancer. BCRP can be associated with clinical cancer drug resistance, in particular acute myelogenous or acute lymphocytic leukemias. The overexpression of BCRP contributes to the resistance of several chemotherapeutic drugs, such as topotecan, methotrexate, mitoxantrone, doxorubicin and daunorubicin. The Food and Drugs Administration has already recognized that BCRP is clinically one of the most important drug transporters, mainly because it leads to a reduction of clinical efficacy of various anticancer drugs through its ATP-dependent drug efflux pump function as well as its apparent participation in drug resistance. This review article aims to summarize the different research findings on marine natural products with BCRP inhibiting activity. In this sense, the potential modulation of physiological targets of BCRP by natural or synthetic compounds offers a great possibility for the discovery of new drugs and valuable research tools to recognize the function of the complex ABC-transporters. 相似文献
7.
Amanda S. Hirata James J. La Clair Paula C. Jimenez Leticia Veras Costa-Lotufo William Fenical 《Marine drugs》2022,20(5)
The bioactive natural product seriniquinone was discovered as a potential melanoma drug, which was produced by the as-yet-undescribed marine bacterium of the rare genus Serinicoccus. As part of a long-term research program aimed at the discovery of new agents for the treatment of cancer, seriniquinone revealed remarkable in vitro activity against a diversity of cancer cell lines in the US National Cancer Institute 60-cell line screening. Target deconvolution studies defined the seriniquinones as a new class of melanoma-selective agents that act in part by targeting dermcidin (DCD). The targeted DCD peptide has been recently examined and defined as a “pro-survival peptide” in cancer cells. While DCD was first isolated from human skin and thought to be only an antimicrobial peptide, currently DCD has been also identified as a peptide associated with the survival of cancer cells, through what is believed to be a disulfide-based conjugation with proteins that would normally induce apoptosis. However, the significantly enhanced potency of seriniquinone was of particular interest against the melanoma cell lines assessed in the NCI 60-cell line panel. This observed selectivity provided a driving force that resulted in a multidimensional program for the discovery of a usable drug with a new anticancer target and, therefore, a novel mode of action. Here, we provided an overview of the discovery and development efforts to date. 相似文献
8.
Lijian Ding Rinat Bar-Shalom Dikla Aharonovich Naoaki Kurisawa Gaurav Patial Shuang Li Shan He Xiaojun Yan Arihiro Iwasaki Kiyotake Suenaga Chengcong Zhu Haixi Luo Fuli Tian Fuad Fares C. Benjamin Naman Tal Luzzatto-Knaan 《Marine drugs》2021,19(7)
Metabolomics can be used to study complex mixtures of natural products, or secondary metabolites, for many different purposes. One productive application of metabolomics that has emerged in recent years is the guiding direction for isolating molecules with structural novelty through analysis of untargeted LC-MS/MS data. The metabolomics-driven investigation and bioassay-guided fractionation of a biomass assemblage from the South China Sea dominated by a marine filamentous cyanobacteria, cf. Neolyngbya sp., has led to the discovery of a natural product in this study, wenchangamide A (1). Wenchangamide A was found to concentration-dependently cause fast-onset apoptosis in HCT116 human colon cancer cells in vitro (24 h IC50 = 38 μM). Untargeted metabolomics, by way of MS/MS molecular networking, was used further to generate a structural proposal for a new natural product analogue of 1, here coined wenchangamide B, which was present in the organic extract and bioactive sub-fractions of the biomass examined. The wenchangamides are of interest for anticancer drug discovery, and the characterization of these molecules will facilitate the future discovery of related natural products and development of synthetic analogues. 相似文献
9.
The resistance of tumor cells to a broad range of anticancer agents continues to be a problem for the success of cancer chemotherapy. Multidrug resistance (MDR) is due in part to three drug transporter proteins: ABCB1/P-glycoprotein (P-gp), ABCC1/multidrug resistance protein 1 (MRP1) and ABCG2/breast cancer resistance protein (BCRP). These transporters are part of the ATP-binding cassette (ABC) superfamily, whose members function as ATP-dependent drug-efflux pumps. Their activity can be blocked by various drugs such as verapamil (calcium channel blocker) and cyclosporin A (immunosuppressive agent), etc. These compounds are called MDR modulators or reversals. This review highlights several marine natural products with reversal effect on multidrug resistance in cancer, including agosterol A, ecteinascidin 743, sipholane triterpenoids, bryostatin 1, and welwitindolinones. 相似文献
10.
Kang JH Song KH Woo JK Park MH Rhee MH Choi C Oh SH 《Plant foods for human nutrition (Dordrecht, Netherlands)》2011,66(3):298-305
Cancer prevention is effective and reduces health care costs because cancer is often a preventable disease that can be affected
by lifestyle factors. Therefore, researchers are interested in discovering natural compounds that have anticancer activities,
such as delaying the development of cancer and preventing its progression. One such natural agent is ginseng (Panax ginseng), which is traditionally used in some parts of the world as a popular remedy for various diseases including cancer. We hypothesized
that the ginsenoside Rp1, a component of ginseng, reduces cancer cell proliferation through inhibition of the insulin-like
growth factor 1 receptor (IGF-1R)/Akt pathway. We first tested the efficacy of Rp1 against human breast cancer cell lines.
Treatment with Rp1 inhibited breast cancer cell proliferation and inhibited both anchorage-dependent and -independent breast
cancer cell colony formation. In addition, treatment with 20 μM Rp1 induced cycle arrest and apoptosis-mediated cell growth
suppression. Our findings further indicated that Rp1 decreased the stability of the IGF-1R protein in breast cancer cells.
Therefore, we suggest that Rp1 has potential as an anticancer drug and that IGF-1R is an important target for treatment and
prevention of breast cancer. 相似文献
11.
Colorectal cancer, a malignant tumor with high mortality, has a poor prognosis due to drug resistance and toxicity in clinical surgery and chemotherapy. Thus, finding safer and more efficient drugs for clinical trials is vital and urgent. Natural marine compounds, with rich resources and original chemical structures, are applied widely in anticancer treatments. We provide a systematic overview of recently reported marine compounds such as alkaloids, peptides, terpenoids, polysaccharides, and carotenoids from in vitro, in vivo, and clinical studies. The in vitro studies summarized the marine origins and pharmacological mechanisms, including anti-proliferation, anti-angiogenesis, anti-migration, anti-invasion, the acceleration of cycle arrest, and the promotion of tumor apoptosis, of various compounds. The in vivo studies outlined the antitumor effects of marine compounds on colorectal cancer model mice and evaluated their efficacy in terms of tumor inhibition, hepatotoxicity, and nephrotoxicity. The clinical studies summarized the major chemical classifications and targets of action of the clinical drugs that have entered clinical approval and completed approval for marine anticancer. In summary, we present the current situation regarding the application of natural anti-colorectal cancer marine compounds and prospects for their clinical application. 相似文献
12.
Tiago Leo Mingxun Wang Nathan Moss Ricardo da Silva Jon Sanders Sergey Nurk Alexey Gurevich Gregory Humphrey Raphael Reher Qiyun Zhu Pedro Belda-Ferre Evgenia Glukhov Syrena Whitner Kelsey L. Alexander Robert Rex Pavel Pevzner Pieter C. Dorrestein Rob Knight Nuno Bandeira William H. Gerwick Lena Gerwick 《Marine drugs》2021,19(1)
Microbial natural products are important for the understanding of microbial interactions, chemical defense and communication, and have also served as an inspirational source for numerous pharmaceutical drugs. Tropical marine cyanobacteria have been highlighted as a great source of new natural products, however, few reports have appeared wherein a multi-omics approach has been used to study their natural products potential (i.e., reports are often focused on an individual natural product and its biosynthesis). This study focuses on describing the natural product genetic potential as well as the expressed natural product molecules in benthic tropical cyanobacteria. We collected from several sites around the world and sequenced the genomes of 24 tropical filamentous marine cyanobacteria. The informatics program antiSMASH was used to annotate the major classes of gene clusters. BiG-SCAPE phylum-wide analysis revealed the most promising strains for natural product discovery among these cyanobacteria. LCMS/MS-based metabolomics highlighted the most abundant molecules and molecular classes among 10 of these marine cyanobacterial samples. We observed that despite many genes encoding for peptidic natural products, peptides were not as abundant as lipids and lipopeptides in the chemical extracts. Our results highlight a number of highly interesting biosynthetic gene clusters for genome mining among these cyanobacterial samples. 相似文献
13.
Marine fungi are known to produce structurally unique secondary metabolites, and more than 1000 marine fungal-derived metabolites have already been reported. Despite the absence of marine fungal-derived metabolites in the current clinical pipeline, dozens of them have been classified as potential chemotherapy candidates because of their anticancer activity. Over the last decade, several comprehensive reviews have covered the potential anticancer activity of marine fungal-derived metabolites. However, these reviews consider the term “cytotoxicity” to be synonymous with “anticancer agent”, which is not actually true. Indeed, a cytotoxic compound is by definition a poisonous compound. To become a potential anticancer agent, a cytotoxic compound must at least display (i) selectivity between normal and cancer cells (ii) activity against multidrug-resistant (MDR) cancer cells; and (iii) a preferentially non-apoptotic cell death mechanism, as it is now well known that a high proportion of cancer cells that resist chemotherapy are in fact apoptosis-resistant cancer cells against which pro-apoptotic drugs have more than limited efficacy. The present review thus focuses on the cytotoxic marine fungal-derived metabolites whose ability to kill cancer cells has been reported in the literature. Particular attention is paid to the compounds that kill cancer cells through non-apoptotic cell death mechanisms. 相似文献
14.
Marilia Barreca Virginia Span Alessandra Montalbano Mercedes Cueto Ana R. Díaz Marrero Irem Deniz Ayegül Erdoan Lada Luki&#x; Bilela Corentin Moulin Elisabeth Taffin-de-Givenchy Filippo Spriano Giuseppe Perale Mohamed Mehiri Ana Rotter Olivier P. Thomas Paola Barraja Susana P. Gaudêncio Francesco Bertoni 《Marine drugs》2020,18(12)
The marine environment is a rich source of biologically active molecules for the treatment of human diseases, especially cancer. The adaptation to unique environmental conditions led marine organisms to evolve different pathways than their terrestrial counterparts, thus producing unique chemicals with a broad diversity and complexity. So far, more than 36,000 compounds have been isolated from marine micro- and macro-organisms including but not limited to fungi, bacteria, microalgae, macroalgae, sponges, corals, mollusks and tunicates, with hundreds of new marine natural products (MNPs) being discovered every year. Marine-based pharmaceuticals have started to impact modern pharmacology and different anti-cancer drugs derived from marine compounds have been approved for clinical use, such as: cytarabine, vidarabine, nelarabine (prodrug of ara-G), fludarabine phosphate (pro-drug of ara-A), trabectedin, eribulin mesylate, brentuximab vedotin, polatuzumab vedotin, enfortumab vedotin, belantamab mafodotin, plitidepsin, and lurbinectedin. This review focuses on the bioactive molecules derived from the marine environment with anticancer activity, discussing their families, origin, structural features and therapeutic use. 相似文献
15.
Worldwide, 19.3 million new cancer cases and almost 10.0 million cancer deaths occur each year. Recently, much attention has been paid to the ocean, the largest biosphere of the earth that harbors a great many different organisms and natural products, to identify novel drugs and drug candidates to fight against malignant neoplasms. The marine compounds show potent anticancer activity in vitro and in vivo, and relatively few drugs have been approved by the U.S. Food and Drug Administration for the treatment of metastatic malignant lymphoma, breast cancer, or Hodgkin′s disease. This review provides a summary of the anticancer effects and mechanisms of action of selected marine compounds, including cytarabine, eribulin, marizomib, plitidepsin, trabectedin, zalypsis, adcetris, and OKI-179. The future development of anticancer marine drugs requires innovative biochemical biology approaches and introduction of novel therapeutic targets, as well as efficient isolation and synthesis of marine-derived natural compounds and derivatives. 相似文献
16.
Marine natural products are a diverse, unique collection of compounds with immense therapeutic potential. This has resulted in these molecules being evaluated for a number of different disease indications including the neglected protozoan diseases, human African trypanosomiasis and Chagas disease, for which very few drugs are currently available. This article will review the marine natural products for which activity against the kinetoplastid parasites; Trypanosoma brucei brucei, T.b. rhodesiense and T. cruzi has been reported. As it is important to know the selectivity of a compound when evaluating its trypanocidal activity, this article will only cover molecules which have simultaneously been tested for cytotoxicity against a mammalian cell line. Compounds have been grouped according to their chemical structure and representative examples from each class were selected for detailed discussion. 相似文献
17.
18.
In the last few decades, the thinning of the ozone layer due to increased atmospheric pollution has exacerbated the negative effects of excessive exposure to solar ultraviolet radiation (UVR), and skin cancer has become a major public health concern. In order to prevent skin damage, public health advice mainly focuses on the use of sunscreens, along with wearing protective clothing and avoiding sun exposure during peak hours. Sunscreens present on the market are topical formulations that contain a number of different synthetic, organic, and inorganic UVR filters with different absorbance profiles, which, when combined, provide broad UVR spectrum protection. However, increased evidence suggests that some of these compounds cause subtle damage to marine ecosystems. One alternative may be the use of natural products that are produced in a wide range of marine species and are mainly thought to act as a defense against UVR-mediated damage. However, their potential for human photoprotection is largely under-investigated. In this review, attention has been placed on the molecular strategies adopted by marine organisms to counteract UVR-induced negative effects and we provide a broad portrayal of the recent literature concerning marine-derived natural products having potential as natural sunscreens/photoprotectants for human skin. Their chemical structure, UVR absorption properties, and their pleiotropic role as bioactive molecules are discussed. Most studies strongly suggest that these natural products could be promising for use in biocompatible sunscreens and may represent an alternative eco-friendly approach to protect humans against UV-induced skin damage. 相似文献
19.
Margarida Costa Mónica Garcia Jo?o Costa-Rodrigues Maria Sofia Costa Maria Jo?o Ribeiro Maria Helena Fernandes Piedade Barros Aldo Barreiro Vitor Vasconcelos Rosário Martins 《Marine drugs》2014,12(1):98-114
The oceans remain a major source of natural compounds with potential in pharmacology. In particular, during the last few decades, marine cyanobacteria have been in focus as producers of interesting bioactive compounds, especially for the treatment of cancer. In this study, the anticancer potential of extracts from twenty eight marine cyanobacteria strains, belonging to the underexplored picoplanktonic genera, Cyanobium, Synechocystis and Synechococcus, and the filamentous genera, Nodosilinea, Leptolyngbya, Pseudanabaena and Romeria, were assessed in eight human tumor cell lines. First, a crude extract was obtained by dichloromethane:methanol extraction, and from it, three fractions were separated in a Si column chromatography. The crude extract and fractions were tested in eight human cancer cell lines for cell viability/toxicity, accessed with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and lactic dehydrogenase release (LDH) assays. Eight point nine percent of the strains revealed strong cytotoxicity; 17.8% showed moderate cytotoxicity, and 14.3% assays showed low toxicity. The results obtained revealed that the studied genera of marine cyanobacteria are a promising source of novel compounds with potential anticancer activity and highlight the interest in also exploring the smaller filamentous and picoplanktonic genera of cyanobacteria. 相似文献
20.
de Andrade Moura L Ortiz-Ramirez F Cavalcanti DN Ribeiro SM Muricy G Teixeira VL Fuly AL 《Marine drugs》2011,9(8):1346-1358
The ischemic disorders, in which platelet aggregation and blood coagulation are involved, represent a major cause of disability and death worldwide. The antithrombotic therapy has unsatisfactory performance and may produce side effects. So, there is a need to seek molecules with antithrombotic properties. Marine organisms produce substances with different well defined ecological functions. Moreover, some of these molecules also exhibit pharmacological properties such as antiviral, anticancer, antiophidic and anticoagulant properties. The aim of this study was to evaluate, through in vitro tests, the effect of two extracts of brown algae and ten marine sponges from Brazil on platelet aggregation and blood coagulation. Our results revealed that most of the extracts were capable of inhibiting platelet aggregation and clotting measured by plasma recalcification tests, prothrombin time, activated partial thromboplastin time, and fibrinogenolytic activity. On the other hand, five of ten species of sponges induced platelet aggregation. Thus, the marine organisms studied here may have molecules with antithrombotic properties, presenting biotechnological potential to antithrombotic therapy. Further chemical investigation should be conducted on the active species to discover useful molecules for the development of new drugs to treat clotting disorders. 相似文献