Extracellular polymeric substance from Aphanizomenon flos-aquae induces apoptosis via the mitochondrial pathway in A431 human epidermoid carcinoma cells

Abstract

Abstract. Extracellular polymeric substance (EPS) is a substance secreted during algal growth, which has been found to have numerous health-promoting effects. In the present study, A431 human epidermoid carcinoma cells were selected as target cells and cultivated in vitro as an experimental model to investigate the anti-cancer effect of extracellular polymeric substances from Aphanizomenon flos-aquae (EPS-A) and the possible underlying mechanism. Apoptosis-and cell cycle-associated molecules as well as the mitochondrial membrane potential of the cells were quantified using flow cytometry (FCM). FCM showed that EPS-A induced cell cycle arrest, which led to a loss of mitochondrial function of the A431 cells and an increase in necrotic and late apoptotic cells. In order to evaluate the apoptosis and cell viability, acridine orange/ethidium bromide staining was used, morphological changes were observed using fluorescence microscopy and typical apoptotic characteristics were observed. Following treatment with a high dose of EPS-A, transmission electron microscopy showed nuclear fragmentation, chromosome condensation, cell shrinkage and expansion of the endoplasmic reticulum; apoptotic bodies were also observed. In conclusion, EPS-A caused cell cycle arrest, stimulated cell apoptosis via the mitochondrial pathway and exhibited important anti-cancer activity.

Strategies to Obtain Designer Polymers Based on Cyanobacterial Extracellular Polymeric Substances (EPS)

“…Initially, the research on cyanobacterial EPS was mainly focused on the potential of these polymers as bioremediation agents for the treatment of industrial and domestic wastewaters, namely for the removal of ammonia, phosphates, and heavy metals [17,18,19,20,46,47,48]. However, as knowledge accumulated, their putative antiviral, antimicrobial, antioxidant, anticoagulant, immunomodulatory, and antitumor activities started to be unveiled [26,29,30,32,33,34,49,50,51,52,53,54,55,56,57,58], opening the way for the use of cyanobacterial EPS in biomedical applications.…”

“…The mechanism of selective cytotoxicity displayed by different EPS with antitumor properties is also being evaluated. Studies performed with EPS isolated from Aphanothece halophytica , Nostoc sphaeroides , Aphanizomenon flosaquae , and Synechocystis ∆ sigF revealed that the antitumor effect of these polymers is due to the induction of apoptosis in the tumor cells [27,34,57,58].…”

Enhanced In Situ Availability of Aphanizomenon Flos-Aquae Constituents Entrapped in Buccal Films for the Treatment of Oxidative Stress-Related Oral Diseases: Biomechanical Characterization and In Vitro/Ex Vivo Evaluation

“…AFA is a filamentous and heterocytic cyanobacterium, commonly found in nutrient-rich freshwaters as one of the dominant species in cyanobacterial bloom [20]. AFA is also called “Klamath algae”, due to its notably growth in the Upper Klamath Lake in Oregon State, USA, and the no longer used term “blue-green algae”, associated to the Cyanobacteria phylum.…”

Pemphigus foliaceus following use of herbal supplement containing Aphanizomenon flos‐aquae

“…However, recent in vitro studies on extracellular polymeric substances from AFA (EPS‐A) expand on alternative apoptotic pathways. EPS‐A has been shown to induce cell cycle arrest and apoptosis via loss of mitochondrial function in A431 epidermoid carcinoma cells . This, in conjunction with cytokine activity, may result in loss of epidermal cell‐to‐cell adhesion and antibody production seen in PF.…”