Yessotoxin, a Marine Toxin, Exhibits Anti-Allergic and Anti-Tumoural Activities Inhibiting Melanoma Tumour Growth in a Preclinical Model

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.

Marine biogenics in sea spray aerosols interact with the mTOR signaling pathway

“…yessotoxin) 13 have been targeted for their pharmaceutical or biotechnological potential 14,15 . Yessotoxin, produced by marine dinoflagellates such as Protoceratium reticulatum , appears to induce apoptotic cell death through the mammalian target of rapamycin (mTOR) pathway 16 and seems to inhibit tumor growth 17 . Combined with other unidentified biogenics in the marine environment, these known bioactive molecules could contribute to beneficial health effects in coastal environments.…”

Biotechnological and Pharmacological Applications of Biotoxins and Other Bioactive Molecules from Dinoflagellates

“…Recently, YTX was found to induce mitotic catastrophe and genetic alterations—which may be of interest for control of tumor progression [ 84 ]. Additionally, Tobío et al [ 85 ] have claimed regression of melanoma tumor cells in mouse cells in vivo, along with negligible toxicity. YTX may also pay a minor role as anti-allergenic and -asthmatic drug, even though the mechanism underlying these therapies remains poorly understood [ 85 ].…”

“…Additionally, Tobío et al [ 85 ] have claimed regression of melanoma tumor cells in mouse cells in vivo, along with negligible toxicity. YTX may also pay a minor role as anti-allergenic and -asthmatic drug, even though the mechanism underlying these therapies remains poorly understood [ 85 ]. YTX seems to interfere with the immune function, since it reduces phagocytic activity on J774 cell line and increases expression of cytokines in J774 phagocyte mammalian cells [ 80 ].…”

Mitotic Catastrophe in BC3H1 Cells following Yessotoxin Exposure

“…Cytotoxic effects vary significantly among cells exposed to it, depending on concentration and time of exposure (de la Rosa et al, 2001 ; Leira et al, 2002 ; Malaguti et al, 2002 ; Alfonso et al, 2003 ; Franchini et al, 2004 ; Callegari and Rossini, 2008 ; Ronzitti and Rossini, 2008 ; Orsi et al, 2010 ; Tubaro et al, 2010 ; Martín-López et al, 2012 ; Pang et al, 2014 ; Fernández-Araujo et al, 2015 ; Ferron et al, 2016 ). Anti-allergic and anti-tumoral activities inhibiting melanoma tumor growth and subacute immunotoxicity has been recently reported (Tobío et al, 2016 ; Ferreiro et al, 2017 ).…”

“…Many authors have proposed therapeutic applications for the marine toxin YTX since it has a broad spectrum of cytotoxic effects (López et al, 2008 , 2011 ; Korsnes, 2012 ; Alfonso et al, 2016 ; Tobío et al, 2016 ). However, its potential as a genotoxic compound has been poorly identified.…”