Abstract

Yessotoxins (YTXs) are a group of marine toxins produced by the dinoflagellates Protoceratium reticulatum, Lingulodinium polyedrum and Gonyaulax spinifera. They may have medical interest due to their potential role as anti-allergic but also anti-cancer compounds. However, their biological activities remain poorly characterized. Here, we show that the small molecular compound YTX causes a slight but significant reduction of the ability of mast cells to degranulate. Strikingly, further examination revealed that YTX had a marked and selective cytotoxicity for the RBL-2H3 mast cell line inducing apoptosis, while primary bone marrow derived mast cells were highly resistant. In addition, YTX exhibited strong cytotoxicity against the human B-chronic lymphocytic leukaemia cell line MEC1 and the murine melanoma cell line B16F10. To analyse the potential role of YTX as an anti-cancer drug in vivo we used the well-established B16F10 melanoma preclinical mouse model. Our results demonstrate that a few local application of YTX around established tumours dramatically diminished tumour growth in the absence of any significant toxicity as determined by the absence of weight loss and haematological alterations. Our data support that YTX may have a minor role as an anti-allergic drug, but reveals an important potential for its use as an anti-cancer drug.

Highlights

  • Yessotoxins (YTXs) are a group of lipophilic marine exotoxins produced by the dinoflagellates Protoceratium reticulatum, Lingulodinium polyedrum and Gonyaulax spinifera [1,2,3]

  • A decrease of the degranulation response was observed in Bone marrow-derived mast cells (BMMCs) after 1h incubation of YTX, independently of whether it had been removed before stimulation or not (Fig 1B, right panel)

  • The inhibitory effect required prolonged preincubation with YTX as it was only observed after pretreatment for 1h, while no effect was observed after 30min (Fig 1B, left panel). These results demonstrate that YTX decreases β-hexosaminidase release, its effect was not very potent reaching with a maximum inhibition of 25% in both BMMCs and rat basophilic leukemia (RBL) cells

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Summary

Introduction

Yessotoxins (YTXs) are a group of lipophilic marine exotoxins produced by the dinoflagellates Protoceratium reticulatum, Lingulodinium polyedrum and Gonyaulax spinifera [1,2,3]. The group of YTXs is composed of close to 90 known analogs (YTX, homoYTX, hydroxyYTX, carboxyYTX and desulfoYTX among others) [4], the chemical structures for most of these compounds remain unclear [1].

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