Cytotoxic Activities and Molecular Mechanisms of the Beauvericin and Beauvericin G1 Microbial Products against Melanoma Cells

Abstract

Melanoma is the most serious type of skin cancer and remains highly drug-resistant. Therefore, the discovery of novel effective agents against melanoma is in high demand. Herein, we investigated the cytotoxic activities in melanoma cells and underlying molecular mechanisms of beauvericin (BEA) and its analogue beauvericin G 1 (BEA G 1 ), which are cyclohexadepsipeptides isolated from fungi. BEA and BEA G 1 significantly suppressed the growth, clonogenicity, migration, and invasion of A375SM human melanoma cells and promoted caspase-dependent apoptosis through upregulation of death receptors, as well as modulation of pro-and anti-apoptotic Bcl-2 family members. Furthermore, the effects of BEA and BEA G 1 were associated with the suppression of multiple molecular targets that play crucial roles in melanoma oncogenesis, including ERK, JNK, p38, NF-κB, STAT3, and MITF. Notably, the cytotoxic efficacy of BEA G 1 against A375SM cells was stronger than that of BEA. These findings suggest that BEA and BEA G 1 can be further investigated as potent cytotoxic natural compounds for the suppression of melanoma progression.

The Mycotoxin Beauvericin Exhibits Immunostimulatory Effects on Dendritic Cells via Activating the TLR4 Signaling Pathway

“…Alternatively, after 24 hours, cell culture supernatants were collected and the IL-12p70 concentration was determined by ELISA assays. 18). Flow cytometry was performed on LSRFortessa (BD Biosciences) or FACSCanto II (BD Biosciences) cytometers.…”

“…Beauvericin is a cyclic hexadepsipeptide, belonging to the enniatin family and is produced by various fungi, such as Beaveria bassiana and Fusarium spp (10,11).. As a mycotoxin, BEA is a very common contaminant of cereal and cereal based products (12,13), but it is also found in other products such as nuts and coffee (14). Multiple and diverse properties of BEA have been reported such as enhancement of pesticide sensitivity (15), antibacterial activity against Gram-positive and Gram-negative bacteria (16), anti-viral activity against human immunodeficiency virus type-1 integrase (17), and cytotoxic activity against melanoma cells (18). BEA can also cause cell apoptosis by inducing reactive oxygen species (ROS) production (19).…”

The mycotoxin Beauvericin exhibits immunostimulatory effects on dendritic cells via activating the TLR4 signaling pathway

“…As a mycotoxin, BEA is a very common contaminant of cereal and cereal based products (12,13), but it is also found in other products such as nuts and coffee (14). Multiple and divers properties of BEA have been reported such as enhancement of pesticide sensitivity (15), anti-bacterial activity against Gram-positive and Gram-negative bacteria (16), anti-viral activity against human immunodeficiency virus type-1 integrase (17), and cytotoxic activity against melanoma cells (18). BEA can also cause cell apoptosis by inducing reactive oxygen species (ROS) production (19).…”

“…The copyright holder for this preprint this version posted January 26, 2022. ; https://doi.org/10.1101/2022.01. 20.476919 doi: bioRxiv preprint been reported such as enhancement of pesticide sensitivity (15), anti-bacterial activity against Gram-positive and Gram-negative bacteria (16), anti-viral activity against human immunodeficiency virus type-1 integrase (17), and cytotoxic activity against melanoma cells (18). BEA can also cause cell apoptosis by inducing reactive oxygen species (ROS) production (19).…”