The Marine Dinoflagellate Alexandrium minutum Activates a Mitophagic Pathway in Human Lung Cancer Cells

Galasso, Christian; Nuzzo, Genoveffa; Brunet, Christophe; Ianora, Adrianna; Sardo, Angela; Fontana, Angelo; Sansone, Clementina

doi:10.3390/md16120502

Cited by 21 publications

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“…Microalgae have already shown to have several bioactivities for the treatment of human pathologies, such as anticancer, anti-inflammatory, anti-diabetes, antioxidant, anti-tuberculosis, anti-epilepsy, anti-hypertensive, anti-atherosclerosis and anti-osteoporosis activities [95,[125][126][127][128]. In particular, Alexandrium minutum has been shown to be active on human lung cancer cells [129], Alexandrium andersoni induces cell death in lung and colorectal tumour cell lines [130], while Alexandrium tamutum was active on human melanoma cell lines [17]. Altogether, these data suggest that Alexandrium spp.…”

Section: Discussionmentioning

confidence: 99%

De novo Transcriptome of the Non-saxitoxin Producing Alexandrium tamutum Reveals New Insights on Harmful Dinoflagellates

et al. 2020

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Many dinoflagellates species, especially of the Alexandrium genus, produce a series of toxins with tremendous impacts on human and environmental health, and tourism economies. Alexandrium tamutum was discovered for the first time in the Gulf of Naples, and it is not known to produce saxitoxins. However, a clone of A. tamutum from the same Gulf showed copepod reproduction impairment and antiproliferative activity. In this study, the full transcriptome of the dinoflagellate A. tamutum is presented in both control and phosphate starvation conditions. RNA-seq approach was used for in silico identification of transcripts that can be involved in the synthesis of toxic compounds. Phosphate starvation was selected because it is known to induce toxin production for other Alexandrium spp. Results showed the presence of three transcripts related to saxitoxin synthesis (sxtA, sxtG and sxtU), and others potentially related to the synthesis of additional toxic compounds (e.g., 44 transcripts annotated as “polyketide synthase”). These data suggest that even if this A. tamutum clone does not produce saxitoxins, it has the potential to produce toxic metabolites, in line with the previously observed activity. These data give new insights into toxic microalgae, toxin production and their potential applications for the treatment of human pathologies.

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Section: Discussionmentioning

confidence: 99%

De novo Transcriptome of the Non-saxitoxin Producing Alexandrium tamutum Reveals New Insights on Harmful Dinoflagellates

et al. 2020

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confidence: 86%

“…Moreover, the glycoconjugate did not reveal a cytotoxicity against human normal lung fibroblasts (WI38), but induced cell death, triggered by mitochondrial autophagy (mitophagy) in tumor cells. No mitophagic events were activated by it in normal WI38 cells [6].Kostetsky et al from the Far East Federal University (Vladivostok, Russia) have compared the fatty acid composition and thermal transitions of membrane lipids from green macroalgae Ulva lactuca, collected in the Sea of Japan and the Adriatic Sea. The adaptation to a warmer climatic zone was accompanied by a significant decrease in the ratio between unsaturated and saturated fatty acids (UFA/SFA) in membrane lipids.…”

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confidence: 99%

“…The diversity of marine glycoconjugate sources and their chemical structures, described in this Special Issue, is impressive. Two articles concern microalgal metabolites such as steroid and sphingoid glycoconjugates, and a glycoprotein from a sea cucumber with interesting biological activities, respectively [5,6]. One article discusses the fatty acid composition and thermotropic behavior of glycolipids and other membrane lipids of green macrophyte Ulva lactuca [7].…”

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Marine Glycoconjugates: Trends and Perspectives

2020

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Glycoconjugates play significant roles in biological systems and are used in medicine, for example as vaccines. Glycoproteins, peptidoglycans, lipopolysaccharides, and other biopolymer glycoconjugates are responsible for cellular interactions, including cell-cell recognition and the binding of cells to the intercellular matrix. These molecules perform signal, antigenic and transport functions, and participate in the formation of receptors and other important membrane and blood constituents. Due to the negative charges of some sulfated glycoconjugates and the binding of water, they are critical for maintaining the physical status of connective tissue [1]. Low molecular weight glycoconjugates, such as triterpene and steroidal glycosides [2][3][4], glycolipids, are also well known as molecules playing important internal and exterior roles. Diverse glycoconjugates show a very wide spectrum of biological activities, including defensive, cytotoxic, antitumor, immunomodulatory, and antioxidant properties. The water environment requires high solubility for signal or anti-predatory exometabolites of marine organisms, and carbohydrate moieties provide this property. All these peculiarities explain the very wide diversity of glycoconjugates of marine origin, including those presented in the current Special Issue.Sterol and sphingolipid glycoconjugates, which are widespread, but insufficiently studied metabolites of microalgae, were discussed by Stonik and Stonik in the review article. Glycosylated sterols play important biological roles in microalgae and show different beneficial properties useful for medicine and healthy food. Dietary sterols and their glycoconjugates of microalgae enter into marine invertebrates through food chains and may be converted into 7(8)-unsaturated sterols and their derivatives, such as polyhydroxylated sterols and, probably, glycosides of starfishes and sea cucumbers. The knowledge of microalgal glycosphingolipids still remains poor, despite intensive investigations. Some of them are important for their interactions with pathogens and may induce apoptosis in microalgae. They also participate in the termination of microalgal blooms [5].In their experimental article, Galasso et al. have discussed the obtaining and properties of a water-soluble bioactive fraction isolated from the toxic dinoflagellate Alexandrium minutem. This substance is a glycoprotein with a molecular weight above 20 kDa. It demonstrates specific antiproliferative activity (IC 50 = 0.4 µg/mL) against the A549 cell line (the human lung adenocarcinoma cells). Moreover, the glycoconjugate did not reveal a cytotoxicity against human normal lung fibroblasts (WI38), but induced cell death, triggered by mitochondrial autophagy (mitophagy) in tumor cells. No mitophagic events were activated by it in normal WI38 cells [6].Kostetsky et al. from the Far East Federal University (Vladivostok, Russia) have compared the fatty acid composition and thermal transitions of membrane lipids from green macroalgae Ulva lactuca, collected in the Sea of...

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“…Apoptosis and autophagy have been extensively studied in several vertebrates, such as Danio rerio (zebrafish), and invertebrates, such as Drosophila melanogaster (fruit fly) and Caenorhabditis elegans (worm) [ 11 , 12 , 13 ]. There is also evidence of in vitro activation of autophagy and apoptosis on human cancer cell lines after exposure to marine compounds [ 14 , 15 , 16 ]. These studies have allowed the identification of potential molecular targets for chemoprevention and chemotherapy [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

Diatom-Derived Polyunsaturated Aldehydes Activate Similar Cell Death Genes in Two Different Systems: Sea Urchin Embryos and Human Cells

Galasso

Celentano

Costantini

et al. 2020

IJMS

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Programmed cell death, such as apoptosis and autophagy, are key processes that are activated early on during development, leading to remodelling in embryos and homeostasis in adult organisms. Genomic conservation of death factors has been largely investigated in the animal and plant kingdoms. In this study, we analysed, for the first time, the expression profile of 11 genes involved in apoptosis (extrinsic and intrinsic pathways) and autophagy in sea urchin Paracentrotus lividus embryos exposed to antiproliferative polyunsaturated aldehydes (PUAs), and we compared these results with those obtained on the human cell line A549 treated with the same molecules. We found that sea urchins and human cells activated, at the gene level, a similar cell death response to these compounds. Despite the evolutionary distance between sea urchins and humans, we observed that the activation of apoptotic and autophagic genes in response to cytotoxic compounds is a conserved process. These results give first insight on death mechanisms of P. lividus death mechanisms, also providing additional information for the use of this marine organism as a useful in vitro model for the study of cell death signalling pathways activated in response to chemical compounds.

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The Marine Dinoflagellate Alexandrium minutum Activates a Mitophagic Pathway in Human Lung Cancer Cells

Cited by 21 publications

References 55 publications

De novo Transcriptome of the Non-saxitoxin Producing Alexandrium tamutum Reveals New Insights on Harmful Dinoflagellates

De novo Transcriptome of the Non-saxitoxin Producing Alexandrium tamutum Reveals New Insights on Harmful Dinoflagellates

Marine Glycoconjugates: Trends and Perspectives

Diatom-Derived Polyunsaturated Aldehydes Activate Similar Cell Death Genes in Two Different Systems: Sea Urchin Embryos and Human Cells

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