Eupalmerin acetate, a novel anticancer agent from Caribbean gorgonian octocorals, induces apoptosis in malignant glioma cells via the c-Jun NH2-terminal kinase pathway (original) (raw)

Small Molecules of Marine Origin as Potential Anti-Glioma Agents

Molecules

Marine organisms are able to produce a plethora of small molecules with novel chemical structures and potent biological properties, being a fertile source for discovery of pharmacologically active compounds, already with several marine-derived agents approved as drugs. Glioma is classified by the WHO as the most common and aggressive form of tumor on CNS. Currently, Temozolomide is the only chemotherapeutic option approved by the FDA even though having some limitations. This review presents, for the first time, a comprehensive overview of marine compounds described as anti-glioma agents in the last decade. Nearly fifty compounds were compiled in this document and organized accordingly to their marine sources. Highlights on the mechanism of action and ADME properties were included. Some of these marine compounds could be promising leads for the discovery of new therapeutic alternatives for glioma treatment.

Novel Marine Compounds: Anticancer or Genotoxic?

Journal of Biomedicine and Biotechnology, 2004

In the past several decades, marine organisms have generously gifted to the pharmaceutical industries numerous naturally bioactive compounds with antiviral, antibacterial, antimalarial, anti-inflammatory, antioxidant, and anticancer potentials. But till date only few anticancer drugs (cytarabine, vidarabine) have been commercially developed from marine compounds while several others are currently in different clinical trials. Majority of these compounds were tested in the tumor xenograft models, however, lack of anticancer potential data in the chemical- and/or oncogene-induced pre-initiation animal carcinogenesis models might have cost some of the marine anticancer compounds an early exit from the clinical trials. This review critically discusses importance of preclinical evaluation, failure of human clinical trials with certain potential anticancer agents, the screening tests used, and choice of biomarkers.

Studies on a Promising Anticancer Molecule of Marine Origin. Results of an Interdisciplinary Study

2009

Poly-APS, a mixture of two of 3-octylpyridinium polymers, including 29 and 99 monomeric units, extracted from the Mediterranean sponge, Haliclona (Reniera) sarai, was demonstrated to exert strong specific and non-toxic acetylcholinesterase inhibition in vitro. Since the first '80s, we found that some tumour types, and in particular lung tumours present overexpression of acetylcholinesterase activity. Acetylcholinesterase is an enzyme associated to the cholinergic signal system, but is also involved in cell-to-cell communication driving embryonic development and in the regulation of several cellular features, such as apoptosis and cell movements, and is present in some tumour cells and biopsies. Cytotoxicity tests on immortalized and primary cell lines derived from lung tumour (NSCLC) showed a poly-APS dose-dependent selective reduction of cell viability, statistically significant. The same cells, exposed to the poly-APS salts exhibited a loss in the mitochondrial potential, showed positive response to the annexin V assay, and to the T-terminal assay, that are specific markers of the apoptotic event. What makes the poly-APS salts promising as anticancer therapy adjuvant is that they, at the concentrations inducing apoptosis in tumour cells, do not affect the viability of lymphocytes isolated from healthy patients. Moreover, three-dimensional cell cultures (spheroids) of tumour cells, on exposure to poly-APS show a decrease in the membrane-linked oligosaccharides, that are responsible for the adhesivity of the metastatic cells. Moreover, no effects were demonstrated on healthy organs, such as heart, liver, kidney of mice treated by poly-APS, and in vivo tumours showed a mass and cellular density significantly reduced. In this promising frame, the need emerges for the isolation of synthetic homologs of poly-APS molecules, in order to start a study for the therapeutical application of the drug.

Marine pharmacology in 2000: Antitumor and cytotoxic compounds

International Journal of Cancer, 2003

During 2000, marine antitumor pharmacology research aimed at the discovery of novel antitumor agents was published in 85 peer-reviewed articles. The purpose of this article is to present a structured review of the antitumor and cytotoxic properties of 143 marine natural products, many of them novel compounds that belong to diverse structural classes, including polyketides, terpenes, steroids and peptides. The organisms yielding these bioactive compounds comprised a taxonomically diverse group of marine invertebrate animals, algae, fungi and bacteria. Antitumor pharmacological studies were conducted with 19 marine natural products in a number of experimental and clinical models that defined or further characterized their mechanisms of action. Potentially promising in vitro cytotoxicity data generated with murine and human tumor cell lines were reported for 124 novel marine chemicals with as yet undetermined mechanisms of action. Noteworthy is the fact that marine anticancer research clearly remains a multinational effort, involving researchers from and the United States. Finally, this 2000 overview of the marine pharmacology literature highlights the fact that the discovery of novel marine antitumor agents continued at the same high level of research activity as during 1998 and 1999.

A neglected natural source for targeting glioblastoma

Natural Product Research, 2019

The cytotoxicity of the methanol extract of the freshwater sponge Ochridaspongia rotunda (Arndt, 1937) (Malawispongiidae) was evaluated by MTT assay at in vitro conditions against three brain tumour cell lines (Neuro-2A, U-251 MG and U-87 MG). The extract was actually found to be most effective against the malignant glioma U-251 MG cells reaching a promising IC 50 value of 1.87±0.09 μg/mL at 96 h. However, it exhibited only a bit of cytotoxicity (IC 50 321.14 ± 11.29 μg/mL, 96 h) towards the normal cells. Also, this sponge extract was 5-fold more selective for U-251 MG versus U-87 MG cells. Finally, monitoring genotoxicity at chromosomal level using the micronucleus test practically revealed lack of any significant toxicity of O. rotunda extract, compared to doxorubicin.

IJSRST1622111 | A Review on Anticancer Drug from Marine

The marine environment is a rich source of both biological and chemical diversity. It is very much likely that marine organisms would be wonderful source of biologically active molecules The collection of the marine therapeutics includes molecules with antibiotic, antiviral, antiphrastic, analgesic and anticancer agent from bacteria, cyanobacteria, tunica, fungi, sponge This reviewfocuses on the latest studies and critical research in this field and evidences the immense potential ofmarine organisms as sources of bioactive peptides and other anticancer biomolecules Various anticancer compounds like Aplidine, Bryostatin-1, Didemin B, Dolastation, Ecteinascidine with diverse modes of action, such as, anti-proliferative, antioxidant, anti-microtubule havebeen isolated from marine sources. Traditional chemotherapeutic agents have a range of side effects likefatigue, gastrointestinal distress and depression of immune system which introduces the these sources have been shown to have antioxidantactivity and cytotoxic effect on several human cancers such as leukemia, lymphoma, ovarian, melanoma, breast, bladder, neuroendocrine, prostatic, colon and non-small cell lung cancer very potently.

Novel Marine Secondary Metabolites Worthy of Development as Anticancer Agents: A Review

Molecules

Secondary metabolites from marine sources have a wide range of biological activity. Marine natural products are promising candidates for lead pharmacological compounds to treat diseases that plague humans, including cancer. Cancer is a life-threatening disorder that has been difficult to overcome. It is a long-term illness that affects both young and old people. In recent years, significant attempts have been made to identify new anticancer drugs, as the existing drugs have been useless due to resistance of the malignant cells. Natural products derived from marine sources have been tested for their anticancer activity using a variety of cancer cell lines derived from humans and other sources, some of which have already been approved for clinical use, while some others are still being tested. These compounds can assault cancer cells via a variety of mechanisms, but certain cancer cells are resistant to them. As a result, the goal of this review was to look into the anticancer potenti...

Anti-tumour drugs of marine origin currently at various stages of clinical trials (review

Oncological diseases for a long time have remained one of the most significant health problems of modern society, which causes great losses in its labour and vital potential. Contemporary oncology still faces unsolved issues as insufficient efficacy of treatment of progressing and metastatic cancer, chemoresistance, and side-effects of the traditional therapy which lead to disabilities among or death of a high number of patients. Development of new anti-tumour preparations with a broad range of pharmaceutical properties and low toxicity is becoming increasingly relevant every year. The objective of the study was to provide a review of the recent data about anti-tumour preparations of marine origin currently being at various phases of clinical trials in order to present the biological value of marine organisms-producers of cytotoxic compounds, and the perspectives of their use in modern biomedical technologies. Unlike the synthetic oncological preparations, natural compounds are safer, have broader range of cytotoxic activity, can inhibit the processes of tumour development and metastasis, and at the same time have effects on several etiopathogenic links of carcinogenesis. Currently, practical oncology uses 12 anti-tumour preparations of marine origin (Fludarabine, Cytarabine, Midostaurin, Nelarabine, Eribulin mesylate, Brentuximab vedotin, Trabectedin, Plitidepsin, Enfortumab vedotin, Polatuzumab vedotin, Belantamab mafodotin, Lurbinectedin), 27 substances are at different stages of clinical trials. Contemporary approaches to the treatment of oncological diseases are based on targeted methods such as immune and genetic therapies, antibody-drug conjugates, nanoparticles of biopolymers, and metals. All those methods employ bioactive compounds of marine origin. Numerous literature data from recent years indicate heightened attention to the marine pharmacology and the high potential of marine organisms for the biomedicinal and pharmaceutic industries.

From Marine Origin to Therapeutics: The Antitumor Potential of Marine Algae-Derived Compounds

Marine environment has demonstrated to be an interesting source of compounds with uncommon and unique chemical features on which the molecular modeling and chemical synthesis of new drugs can be based with greater efficacy and specificity for the therapeutics. Cancer is a growing public health threat, and despite the advances in biomedical research and technology, there is an urgent need for the development of new anticancer drugs. In this field, it is estimated that more than 60% of commercially available anticancer drugs are natural biomimetic inspired. Among the marine organisms, algae have revealed to be one of the major sources of new compounds of marine origin, including those exhibiting antitumor and cytotoxic potential. These compounds demonstrated ability to mediate specific inhibitory activities on a number of key cellular processes, including apoptosis pathways, angiogenesis, migration and invasion, in both in vitro and in vivo models, revealing their potential to be used as anticancer drugs. This review will focus on the bioactive molecules from algae with antitumor potential, from their origin to their potential uses, with special emphasis to the alga Sphaerococcus coronopifolius as a producer of cytotoxic compounds.