The investigation of epsilon toxin effects on different cancerous cell lines and its synergism effect with methotrexate

Shekarsaraei, Azin Gholami; Hasannia, Sadegh; Pirooznia, Nazanin; Ataiee, Fariba

doi:10.4103/0973-1482.131338

Cited by 2 publications

(2 citation statements)

References 28 publications

(47 reference statements)

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“…Among the bacterial pore-forming toxins which were investigated for their cytolytic or cytocidal properties against tumorous cells were α-hemolysin of Staphylococcus aureus [26,301,302,303], parasporin-4 of Bacillus thuringiensis [304,305,306,307], listeriolysin O of Listeria monocytogenes [308], aerolysin of Aeromonas hydrophila [309,310], the S component of Panton-Valentine lekocidin (LukS-PV) of Staphylococcus aureus [311] and epsilon toxin of Clostridium perfringens [312]. In particular, Bayley and colleagues explored αHL mutants in which channel-forming activity can be triggered or switched on and off by biochemical, chemical, or physical stimuli [26,301,302].…”

Section: Channel-forming Bacterial Toxins For Cancer Therapymentioning

confidence: 99%

Channel-Forming Bacterial Toxins in Biosensing and Macromolecule Delivery

Gurnev

Nestorovich

2014

Toxins

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To intoxicate cells, pore-forming bacterial toxins are evolved to allow for the transmembrane traffic of different substrates, ranging from small inorganic ions to cell-specific polypeptides. Recent developments in single-channel electrical recordings, X-ray crystallography, protein engineering, and computational methods have generated a large body of knowledge about the basic principles of channel-mediated molecular transport. These discoveries provide a robust framework for expansion of the described principles and methods toward use of biological nanopores in the growing field of nanobiotechnology. This article, written for a special volume on “Intracellular Traffic and Transport of Bacterial Protein Toxins”, reviews the current state of applications of pore-forming bacterial toxins in small- and macromolecule-sensing, targeted cancer therapy, and drug delivery. We discuss the electrophysiological studies that explore molecular details of channel-facilitated protein and polymer transport across cellular membranes using both natural and foreign substrates. The review focuses on the structurally and functionally different bacterial toxins: gramicidin A of Bacillus brevis, α-hemolysin of Staphylococcus aureus, and binary toxin of Bacillus anthracis, which have found their “second life” in a variety of developing medical and technological applications.

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Section: Channel-forming Bacterial Toxins For Cancer Therapymentioning

confidence: 99%

Channel-Forming Bacterial Toxins in Biosensing and Macromolecule Delivery

Gurnev

Nestorovich

2014

Toxins

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“…The pore formation induced by epsilon toxin was thought to be associated with cytotoxicity [10]. Epsilon toxin has been shown to induce cytotoxicity in various normal and cancer cell lines [11,12]. Increased attention has been given to the potential biological activities of bacterial toxins in triggering intracellular signaling pathways [13].…”

Section: Introductionmentioning

confidence: 99%

Epsilon Toxin Induces Cytotoxicity by Mediating Autophagy and Apoptosis Processes via the PI3K/AKT/mTOR Signaling Pathway in A549 Cells

Dashti,

Hosseini,

Mirhosseini

2024

Preprint

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Background Epsilon toxin, synthesized by Clostridium perfringens, is a toxin from the class of pore-forming proteins that are associated with the development of enterotoxaemia in ruminants. As an agent of bioterrorism, exposure of toxin aerosol form causes endothelial cell damage and cytotoxicity in human lung cells. However, little information is available regarding the cytotoxicity and the mechanisms associated with lung cancer cell lines. The aim of the present study was to explore the cytotoxic effects of epsilon toxin on the human lung cell line A549 and its involvement in the PI3K/AKT/mTOR signaling pathway to clarify the underlying molecular mechanism. Methods and Results Following treatment of A549 cells with epsilon toxin, the cytotoxicity by the MTT and LDH assays and the levels of reactive oxygen species (ROS), cell cycle, and cell apoptosis using flow cytometry assay as well as detection of cell apoptosis with Hoechst 33258 staining were conducted. The expression levels of apoptosis-, autophagy- and PI3K/Akt/mTOR signaling-related mRNA and proteins were measured by qRT-PCR and Western blot analysis. Epsilon toxin concentration-dependently induced a reduction in cell viability and an increase in membrane leakage along with ROS generation. Epsilon toxin upregulated the levels of beclin-1, LC3 II/I, and p62 expression while downregulated the PI3K/Akt/mTOR expression levels. Epsilon toxin significantly arrested cell-cycle at the Sub-G1 phase and could further promote apoptosis in A549 cells via increasing the expression level of P53, Bax and caspase-3 while reducing the expression of Bcl-2, confirmed with annexin V/PI and Hoechst 33258 staining. Conclusions These findings demonstrated that the epsilon toxin-induced cytotoxicity associated with apoptosis and autophagy processes via the PI3K/AKT/mTOR signaling pathway.

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The investigation of epsilon toxin effects on different cancerous cell lines and its synergism effect with methotrexate

Abstract: These finding proposed that due to the ease of local accessibility of lung tumors with aerosol drug delivery, biotoxins can directly be used with chemotherapy drugs in aerosol form.

Cited by 2 publications

References 28 publications

Channel-Forming Bacterial Toxins in Biosensing and Macromolecule Delivery

Channel-Forming Bacterial Toxins in Biosensing and Macromolecule Delivery

Epsilon Toxin Induces Cytotoxicity by Mediating Autophagy and Apoptosis Processes via the PI3K/AKT/mTOR Signaling Pathway in A549 Cells

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