Mitotic Catastrophe in BC3H1 Cells following Yessotoxin Exposure

Abstract

The marine toxin yessotoxin (YTX) can cause various cytotoxic effects depending on cell type and cell line. It is well known to trigger distinct mechanisms for programmed cell death which may overlap or cross-talk. The present contribution provides the first evidence that YTX can cause genotoxicity and induce mitotic catastrophe which can lead to different types of cell death. This work also demonstrates potential information gain from non-intrusive computer-based tracking of many individual cells during long time. Treatment of BC3H1 cells at their exponential growth phase causes atypical nuclear alterations and formation of giant cells with multiple nuclei. These are the most prominent morphological features of mitotic catastrophe. Giant cells undergo slow cell death in a necrosis-like manner. However, apoptotic-like cell death is also observed in these cells. Electron microscopy of treated BC3H1 cells reveal uncondensed chromatin and cells with double nuclei. Activation of p-p53, p-H2AX, p-Chk1, p-ATM, and p-ATR and down-regulation of p-Chk2 indicate DNA damage response and cell cycle deregulation. Micronuclei formation further support this evidence. Data from tracking single cells reveal that YTX treatment suppresses a second round of cell division in BC3H1 cells. These findings suggest that YTX can induce genomic alterations or imperfections in chromosomal segregation leading to permanent mitotic failure. This understanding extends the list of effects from YTX and which are of interest to control cancer and tumor progression.

Single-Cell Tracking of A549 Lung Cancer Cells Exposed to a Marine Toxin Reveals Correlations in Pedigree Tree Profiles

“…Single-cell tracking directly indicates that yessotoxin is genotoxic for A549 cells. Korsnes and Korsnes ( 23 ) showed similar effects for BC3H1 cells. A sign of genotoxicity for cells exposed to a toxin is that they tend to exhibit aberrant mitosis and multipolar divisions ( 29 , 41 – 44 ).…”

“…YTX exposure tends to make A549 cells to delay a second round of mitosis. Korsnes and Korsnes ( 23 ) showed a similar effect on BC3H1 cells and which indicates genotoxicity. Figure 17 shows the distribution of observed life span of cells after the first and second cell division.…”

“…YTX can trigger a broad spectrum of cytotoxic responses ( 13 – 21 ). It can also cause anti-allergic and anti-tumoral effects ( 22 ) and Korsnes and Korsnes ( 23 ) demonstrated its ability to induce genotoxic effects in BC3H1 cells. Several authors have proposed YTX for biotechnological, pharmaceutical, and therapeutic applications due its various cytotoxic and genotoxic effects ( 4 , 24 – 27 ).…”

Novel Insights on the Toxicity of Phycotoxins on the Gut through the Targeting of Enteric Glial Cells

“…A slight decrease of cells in G2/M combined with a slight increase of cells in G0/G1 was induced with YTX that could be a reflection that cells were entering into a repairing state. Although DNA repair involvement has been shown with OA [84] and YTX [85], further investigation is needed to explain these differences.…”

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

“…selective disruption of F-actin microfilaments) [ 80 , 81 ], and fragmentation of adhesion proteins (specifically E-cadherin) [ 82 ], are among the reported YTX effects—dependent on cell line used and treatment duration [ 83 ]. 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.…”