Yessotoxin as a tool to study induction of multiple cell death pathways

Abstract

This work proposes to use the marine algal toxin yessotoxin (YTX) to establish reference model experiments to explore medically valuable effects from induction of multiple cell death pathways. YTX is one of few toxins reported to make such induction. It is a small molecule compound which at low concentrations can induce apoptosis in primary cultures, many types of cells and cell lines. It can also induce a non-apoptotic form of programmed cell death in BC3H1 myoblast cell lines. The present contribution reviews arguments that this type of induction may have principal interest outside this particular example. One principal effect of medical interest may be that cancer cells will not so easily adapt to the synergistic effects from induction of more than one death pathway as compared to induction of only apoptosis.

Keywords: apoptosis; cancer; multiple signalling pathways; neurodegenerative diseases; paraptosis; yessotoxin.

Figure 1

Activation of apoptosis and paraptosis like-cell death in BC3H1 myoblast cell lines to 100 nM YTX. Left: untreated cells. Centre and right: exposed cells after 48 h and 72 h (respectively) showing morphological traits of apoptosis (green arrow) and paraptosis (red arrow). Scale bar: 100 µm.

Figure 2

Apoptotic and paraptotic features in BC3H1 myoblast cell lines exposed to 100 nM YTX. Exposure times are 24 h (left), 48 h (centre) and 72 h (right). Membrane blebbing and apoptotic bodies (green arrow), cytoplasmic vacuolation (red arrow). Note that apoptotic and paraptotic features are already evident at 24 h YTX exposure. Each of the lower image is an enlarged subset of the image above. Scale bar: 100 µm.