The venom and the toxicity of Pelagia noctiluca (Cnidaria: Scyphozoa). A review of three decades of research in Italian laboratories and future perspectives

Recurrent outbreaks of Pelagia noctiluca and health problems consequent to stings were recorded during the last decades. This phenomenon forced some Italian University laboratories to study this cnidarian. The first studies concerned the distribution, biochemical composition and morphology of nematocysts of Pelagia noctiluca. The discharge mechanism of nematocysts was defined starting from early 1980s when enzymes, cations, anions, and pH were observed to have an influence on this process. Notably, trypsin, extreme pH values, some anions (I–, Cl–, SCN–), and thioglycolate were seen to induce, while La3+ and Gd3+ to prevent, nematocyst discharge. The discharge of both in situ and isolated nematocyst was found to be Ca2+ dependent. Furthermore, Pelagia noctiluca nematocysts were seen to retain their discharging capacity in distilled water. The toxicological evaluations were carried out mainly using the crude venom from Pelagia noctiluca because, unfortunately, to date the composition of venom remains unknown. Hemolytic and cytotoxic properties of crude venom have been evaluated on erythrocytes and cultured guinea-pig fibroblasts, mouse fibroblasts, and cancer (neuroblastoma) cells. The activity of Pelagia noctiluca venom on other cnidarians has been also assessed. The crude venom induced apoptosis by reactive oxygen species generation and decrease in mitochondrial transmembrane potential, loss of mitochondrial integrity, and alteration of cell membrane permeability. A pore-forming action mechanism on mitochondrial membrane with oxidative damage was also suggested. The protective activity of some compounds against envenomations has been also evaluated. Future challenges will concern the attempts to characterize the venom and to perform a wider screening of cytotoxicity induced to normal and cancer cells.

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Faculty Opinions recommendation of alpha-Synuclein overexpression during manganese-induced apoptosis in SH-SY5Y neuroblastoma cells.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1283996.751104 ◽

2009 ◽

Author(s):

Michael Aschner

Keyword(s):

Neuroblastoma Cells ◽

Alpha Synuclein ◽

Induced Apoptosis

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Advances in Nanoparticles as Anticancer Drug Delivery Vector: Need of this Century

Current Pharmaceutical Design ◽

10.2174/1381612826666200203124330 ◽

2020 ◽

Vol 26 (15) ◽

pp. 1637-1649 ◽

Cited By ~ 3

Author(s):

Imran Ali ◽

Sofi D. Mukhtar ◽

Heyam S. Ali ◽

Marcus T. Scotti ◽

Luciana Scotti

Keyword(s):

Drug Delivery ◽

Anticancer Drug ◽

Medical Science ◽

Drug Carriers ◽

Anticancer Drug Delivery ◽

Ph Values ◽

Delivery Vector ◽

Future Challenges ◽

Smart Drug ◽

Smart Drug Delivery

Background: Nanotechnology has contributed a great deal to the field of medical science. Smart drugdelivery vectors, combined with stimuli-based characteristics, are becoming increasingly important. The use of external and internal stimulating factors can have enormous benefits and increase the targeting efficiency of nanotechnology platforms. The pH values of tumor vascular tissues are acidic in nature, allowing the improved targeting of anticancer drug payloads using drug-delivery vectors. Nanopolymers are smart drug-delivery vectors that have recently been developed and recommended for use by scientists because of their potential targeting capabilities, non-toxicity and biocompatibility, and make them ideal nanocarriers for personalized drug delivery. Method: The present review article provides an overview of current advances in the use of nanoparticles (NPs) as anticancer drug-delivery vectors. Results: This article reviews the molecular basis for the use of NPs in medicine, including personalized medicine, personalized therapy, emerging vistas in anticancer therapy, nanopolymer targeting, passive and active targeting transports, pH-responsive drug carriers, biological barriers, computer-aided drug design, future challenges and perspectives, biodegradability and safety. Conclusions: This article will benefit academia, researchers, clinicians, and government authorities by providing a basis for further research advancements.

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Apoptosis in human cultured trophoblasts is enhanced by hypoxia and diminished by epidermal growth factor

AJP Cell Physiology ◽

10.1152/ajpcell.2000.278.5.c982 ◽

2000 ◽

Vol 278 (5) ◽

pp. C982-C988 ◽

Cited By ~ 145

Author(s):

Roni Levy ◽

Steven D. Smith ◽

Kala Chandler ◽

Yoel Sadovsky ◽

D. Michael Nelson

Keyword(s):

Cell Differentiation ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Fetal Growth ◽

Fetal Growth Restriction ◽

Caspase Inhibitor ◽

Trophoblast Differentiation ◽

Epidermal Growth ◽

Induced Apoptosis

Preeclampsia and fetal growth restriction are associated with placental hypoperfusion and villous hypoxia. The villous response to this environment includes diminished trophoblast differentiation and enhanced apoptosis. We tested the hypothesis that hypoxia induces apoptosis in cultured trophoblasts, and that epidermal growth factor (EGF), an enhancer of trophoblast differentiation, diminishes hypoxia-induced apoptosis. Trophoblasts isolated from placentas of term-uncomplicated human pregnancies were cultured up to 72 h in standard ([Formula: see text]= 120 mmHg) or hypoxic ([Formula: see text] < 15 mmHg) conditions. Exposure to hypoxia for 24 h markedly enhanced trophoblast apoptosis as determined by DNA laddering, internucleosomal in situ DNA fragmentation, and histomorphology, as well as by the reversibility of the apoptotic process with a caspase inhibitor. Apoptosis was accompanied by increased expression of p53 and Bax and decreased expression of Bcl-2. Addition of EGF to cultured trophoblasts or exposure of more differentiated trophoblasts to hypoxia significantly lowered the level of apoptosis. We conclude that hypoxia enhances apoptosis in cultured trophoblasts by a mechanism that involves an increase in p53 and Bax expression. EGF and enhancement of cell differentiation protect against hypoxic-induced apoptosis.

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MycN sensitizes neuroblastoma cells for drug-induced apoptosis

Oncogene ◽

10.1038/sj.onc.1202435 ◽

1999 ◽

Vol 18 (7) ◽

pp. 1479-1486 ◽

Cited By ~ 84

Author(s):

Simone Fulda ◽

Werner Lutz ◽

Manfred Schwab ◽

Klaus-Michael Debatin

Keyword(s):

Neuroblastoma Cells ◽

Drug Induced ◽

Induced Apoptosis

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Brain-derived neurotrophic factor exerts neuroprotective actions against amyloid β-induced apoptosis in neuroblastoma cells

Experimental and Therapeutic Medicine ◽

10.3892/etm.2014.2033 ◽

2014 ◽

Vol 8 (6) ◽

pp. 1891-1895 ◽

Cited By ~ 15

Author(s):

JIN HEE KIM

Keyword(s):

Neurotrophic Factor ◽

Neuroblastoma Cells ◽

Amyloid Β ◽

Brain Derived Neurotrophic Factor ◽

Neuroprotective Actions ◽

Induced Apoptosis

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Resistance to TRAIL-induced apoptosis in neuroblastoma cells correlates with a loss of caspase-8 expression

Medical and Pediatric Oncology ◽

10.1002/1096-911x(20001201)35:6<603::aid-mpo24>3.0.co;2-1 ◽

2000 ◽

Vol 35 (6) ◽

pp. 603-607 ◽

Cited By ~ 36

Author(s):

Angelika Eggert ◽

Michael A. Grotzer ◽

Tycho J. Zuzak ◽

Barbara R. Wiewrodt ◽

Naohiko Ikegaki ◽

...

Keyword(s):

Neuroblastoma Cells ◽

Caspase 8 ◽

Induced Apoptosis

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Tailoring photosensitive ROS for advanced photodynamic therapy

Experimental & Molecular Medicine ◽

10.1038/s12276-021-00599-7 ◽

2021 ◽

Author(s):

Duc Loc Sai ◽

Jieun Lee ◽

Duc Long Nguyen ◽

Young-Pil Kim

Keyword(s):

Photodynamic Therapy ◽

Reactive Oxygen Species Generation ◽

Cost Effective ◽

Molecular Medicine ◽

Oxygen Species ◽

Significant Progress ◽

Tumor Treatment ◽

Innovative Strategies ◽

Tumor Microenvironments ◽

Future Challenges

AbstractPhotodynamic therapy (PDT) has been considered a noninvasive and cost-effective modality for tumor treatment. However, the complexity of tumor microenvironments poses challenges to the implementation of traditional PDT. Here, we review recent advances in PDT to resolve the current problems. Major breakthroughs in PDTs are enabling significant progress in molecular medicine and are interconnected with innovative strategies based on smart bio/nanomaterials or therapeutic insights. We focus on newly developed PDT strategies designed by tailoring photosensitive reactive oxygen species generation, which include the use of proteinaceous photosensitizers, self-illumination, or oxygen-independent approaches. While these updated PDT platforms are expected to enable major advances in cancer treatment, addressing future challenges related to biosafety and target specificity is discussed throughout as a necessary goal to expand the usefulness of PDT.

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Scrapie prion proteins accumulate in the cytoplasm of persistently infected cultured cells.

The Journal of Cell Biology ◽

10.1083/jcb.110.6.2117 ◽

1990 ◽

Vol 110 (6) ◽

pp. 2117-2132 ◽

Cited By ~ 192

Author(s):

A Taraboulos ◽

D Serban ◽

S B Prusiner

Keyword(s):

Cultured Cells ◽

Prion Diseases ◽

Neuroblastoma Cells ◽

Brain Cell ◽

Cellular Prion Protein ◽

Intracellular Accumulation ◽

Golgi Stack ◽

Glycosyl Phosphatidylinositol ◽

The Central Nervous System

The cellular prion protein (PrPC) is a sialoglycoprotein anchored to the external surface of cells by a glycosyl phosphatidylinositol moiety. During scrapie, an abnormal PrP isoform designated PrPSc accumulates, and much evidence argues that it is a major and necessary component of the infectious prion. Based on the resistance of native PrPSc to proteolysis and to digestion with phosphatidylinositol-specific phospholipase C as well as the enhancement of PrPSc immunoreactivity after denaturation, we devised in situ immunoassays for the detection of PrPSc in cultured cells. Using these immunoassays, we identified the sites of PrPSc accumulation in scrapie-infected cultured cells. We also used these immunoassays to isolate PrPSc-producing clones from a new hamster brain cell line (HaB) and found an excellent correlation between their PrPSc content and prion infectivity titers. In scrapie-infected HaB cells as well as in scrapie-infected mouse neuroblastoma cells, most PrPSc was found to be intracellular and most localized with ligands of the Golgi marker wheat germ agglutinin. In one scrapie-infected HaB clone, PrPSc also localized extensively with MG-160, a protein resident of the medial-Golgi stack whereas this colocalization was not observed in another subclone of these cells. Whether the sites of intracellular accumulation of PrPSc are limited to a few subcellular organelles or they are highly variable remains to be determined. If the intracellular accumulation of PrPSc is found in the cells of the central nervous system, then it might be responsible for the neuronal dysfunction and degeneration which are cardinal features of prion diseases.

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