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What’s lurking beneath the surface?

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Tags: Toxicology

Cyanobacteria are a phylum of bacteria also referred to as blue-green algae. They rely on the production of energy through photosynthesis and produce gaseous oxygen as a by-product. For this reason, they are often deemed responsible for both the conversion of Earth’s atmosphere into an oxidizing one 3.5 billion years ago and the stimulation of biodiversity. They are naturally found in freshwater lakes, ponds and slow-moving streams. Under certain environmental conditions such as water pollution and depending on the genera, cyanobacteria population can explode suddenly and cause harmful algal blooms (HABs). These HABs produce neurotoxins, cytotoxins, endotoxins and hepatotoxins termed cyanotoxins, which can pose a danger to humans and animals. Indeed, some of these cyanotoxins are very powerful poisons capable of causing rapid death by respiratory failure. They can be grouped into three large groups: amino acids (e.g. BMAA), cyclic peptides (e.g. microcystins and nodularins) and alkaloids (e.g. anatoxins, lipopolysaccharides and saxitoxins).


Belonging to the latter, cylindrospermopsin (CYN) is a potent cyanotoxin first identified as the probable cause of a severe case of human poisoning from a local drinking water supply in Australia in 1979. It is produced by several species of freshwater cyanobacteria. It was described as being toxic to liver and kidney although its precise mechanism of toxicity remains poorly understood. Several researchers have since then tried to shed some light on the mode of action of this toxin. Exposure to cylindrospermopsin is, in most cases, ingested orally. Consequently, Dr. Huguet and colleagues from the French Agency for Food, Environmental and Occupational Health and Safety conducted a transcriptomic analysis of human intestinal Caco-2 cells exposed to CYN to identify key cytotoxic players. Using a subtoxic concentration of CYN (1.6µM for 24 hours), they demonstrated that 522 genes involved in 22 biological processes and 50 genes involved in 3 biological processes were up- and down-regulated, respectively. They also revealed that most of these biological processes were involved in (A) growth arrest with the down-regulation of CDKN1a and UHRF1, (B) DNA repair with the up-regulation of Aprataxin and PMS2, and (C) chromatin remodeling with the up-regulation of MYST1, KAT5 and EHMT2.

More recently, Dr. Straser and collaborators from the Slovenian National Institute of Biology investigated the consequences of treating human liver hepatocellular carcinoma HepG2 cells with Enzo’s cylindrospermopsin. A dose-dependent intracellular formation of reactive oxygen species (ROS), which increased steadily over a period of five hours following treatment with subtoxic concentrations of CYN (0-0.5µg/ml), was achieved. Using unmodified and modified comet assays to measure DNA damage and oxidative DNA damage, they demonstrated however that the increase in DNA strand breaks was unlikely to be due to oxidative stress. Finally, CYN significantly increased the mitochondrial membrane potential while no increase in the caspase 3 and 7 activity and in the number of apoptotic cells were obtained. These data suggest that DNA damage combined with the lack of apoptosis following treatment with non-cytotoxic concentrations of CYN may actually enhance its dangerousness with boosted risks of mutations and tumorigenesis. Altogether, these studies highlight the need for further work to completely understand the cytotoxicity of these toxins and discover new therapeutic avenues to counteract them.

Enzo Life Sciences offers a comprehensive portfolio of cyanotoxins including cylindrospermopsin as well as tools to study their cytotoxic effects, some of which are listed below:

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  1. A. Huguet, et al. Modulation of chromatin remodeling induced by the freshwater cyanotoxin cylindrospermopsin in human intestinal caco-2 cells. PLoS One (2014) 9, e99121.
  2. A. Straser, et al. The influence of cylindrospermopsin on oxidative DNA damage and apoptosis induction in HepG2 cells. Chemosphere (2013) 92, 24.

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