Brevilaterin B from Brevibacillus laterosporus has selective antitumor activity and induces apoptosis in epidermal cancer

Abstract

Brevibacillus laterosporus, a newly discovered genus, had been shown to be one of the best candidates for producing multiple antimicrobial peptides (AMPs). Herein, we discovered a new bioactivity of Brevilaterin B, an AMP produced by Br. laterosporus S62-9, and investigated the details about its Anticancer. Proliferation, membrane permeability and apoptotic rate were checked using CCK-8 Assay, LDH Assay and Annexin V-FITC/PI Kits. ROS levels and mitochondrial membrane potential were detected using the uorescent probe DCFH-DA and JC-1. Brevilaterin B exhibited broad anticancer activity in a dose-dependent manner. It selectively inhibited the proliferation of epidermal cancer cell A431 but had no effect on normal cells at 2 µg/mL. Typical morphological characteristics of apoptosis and an apoptotic ratio of 71.0% in A431 were observed after treatment with 2-3 µg/mL of Brevilaterin B. In A431 cells, 21.3% ROS generated and 48.8% reduction in mitochondrial membrane potential further occurred, indicating the main site of action was the mitochondrion. Brevilaterin B secreted by Br. laterosporus S62-9 has potential application as an anticancer medicament, increasing its commercial value. It's believed to be the rst report of the anticancer activity of this type of AMPs. HighlightsBrevilaterin B was rst report to exhibit anticancer activity. Brevilaterin B induces apoptosis of epidermal cancer cell by action on mitochondrion.Brevilaterin B has potential application as an anticancer medicament.

Novel Property Cytotoxicity and Mechanism of Food Preservative Brevilaterins against Human Gastric Cancer Cells

“…This approach has been widely employed in various studies and is considered a robust tool for monitoring apoptosis in vitro and in vivo. As evidenced by our previous research, BB/BC could induce apoptosis in epidermal carcinoma cells A431, with a remarkable apoptotic rate exceeding 70% [ 14 , 15 ]. Moreover, AMPs from various origins, including ranatuerin-2PLx and temporin-1CEa, were found to elevate the apoptotic rate during the induction of cell apoptosis in PC-3 M and Bcap-37 cell lines [ 23 , 24 ].…”

“…In this study, we aimed to investigate the impact of BB/BC, a spectrum anticancer peptide [ 14 , 15 ], on gastric cancer cells. Our results showed that BB/BC strongly inhibited cell proliferation in a dose-dependent manner ( Figure 1 ).…”

“…laterosporus S62-9, as a promising new class of molecules with potent anticancer activity. Indeed, Brevilaterins could display variable inhibition towards 27 cancer cells in a dose-dependent manner [ 14 , 15 ]. In this study, we specifically focused on the inhibitory effects of Brevilaterins on gastric cancer cells and described their properties as potential anticancer agents.…”

“…These bacteria cover the majority of representative food-borne pathogens and spoilage bacteria commonly found in different foods [ 13 ]. Furthermore, our previous investigations have also revealed that Brevilaterins have the potential to effectively inhibit the proliferation of 27 human cancer cell lines, with a particularly strong inhibitory effect against gastric cancer cells [ 14 , 15 ]. However, the detailed anticancer characteristics and mechanisms of Brevilaterins against gastric cancer cells remain unclear and warrant further investigation.…”

Anti-Cancer and Anti-Inflammatory Activities of a Short Molecule, PS14 Derived from the Virulent Cellulose Binding Domain of Aphanomyces invadans, on Human Laryngeal Epithelial Cells and an In Vivo Zebrafish Embryo Model

“…PS14 treatment showed a dose-dependent increase in the concentration of LDH release than the control. Similarly, a peptide named Brevilaterin B, which was derived from Brevibacillus laterosporus , has been shown to cause cell membrane damage, which leads to increased LDH release to the medium [ 25 ]. Based on these reported observations and the outcomes from PS14 challenge, it is evident that PS14 damages the Hep-2 cell membrane.…”