Two Trichothecene Mycotoxins from Myrothecium roridum Induce Apoptosis of HepG-2 Cells via Caspase Activation and Disruption of Mitochondrial Membrane Potential

Abstract

Trichothecene mycotoxins are a type of sesquiterpenoid produced by various kinds of plantpathogenic fungi. In this study, two trichothecene toxins, namely, a novel cytotoxic epiroridin acid and a known trichothecene, mytoxin B, were isolated from the endophytic fungus Myrothecium roridum derived from the medicinal plant Pogostemon cablin. The two trichothecene mytoxins were confirmed to induce the apoptosis of HepG-2 cells by cytomorphology inspection, DNA fragmentation detection, and flow cytometry assay. The cytotoxic mechanisms of the two mycotoxins were investigated by quantitative real time polymerase chain reaction, western blot, and detection of mitochondrial membrane potential. The results showed that the two trichothecene mycotoxins induced the apoptosis of cancer cell HepG-2 via activation of caspase-9 and caspase-3, up-regulation of bax gene expression, down-regulation of bcl-2 gene expression, and disruption of the mitochondrial membrane potential of the HepG-2 cell. This study is the first to report on the cytotoxic mechanism of trichothecene mycotoxins from M. roridum. This study provides new clues for the development of attenuated trichothecene toxins in future treatment of liver cancer.

Mytoxin B and Myrothecine A Induce Apoptosis in Human Hepatocarcinoma Cell Line SMMC-7721 via PI3K/Akt Signaling Pathway

“…They proposed that ROS may be a critical initiator of trichothecin-induced apoptosis in HepG2 cells [29]. Ye et al also found that increasing of the mitochondrial membrane permeability and loss of the mitochondrial membrane potential enhanced the apoptosis rate significantly in HepG-2 cells after treatment with mytoxin B or epiroridin acid for 24 h [14].…”

“…Trichothecene macrolides are valuable leading compounds, and many studies on their structure and anticancer activity have been carried out in recent years [11,12,13]. However, there were few reports concerning their anticancer mechanism [14,15], especially anticancer mechanism of 10,13-cyclotrichothecane derivatives, which were found mainly in symbiotic fungi. Mytoxin B (bearing a 12,13-epoxy group in the sesquiterpene residue) and myrothecine A (a 10,13-cyclotrichothecane derivative of mytoxin B) (Figure 1) are two trichothecene macrolides isolated from endophyte Myrothecium roridum IFB-E012 [1].…”

Intracellular ethanol‐mediated oxidation and apoptosis in HepG2/CYP2E1 cells impaired by two active peptides from seahorse (Hippocampus kuda bleeler) protein hydrolysates via the Nrf2/HO‐1 and akt pathways

“…Apoptosis may be activated by an intrinsic or extrinsic pathway. Apoptosis is regulated by various molecules, such as the bcl‐2 family and cysteinyl aspartate‐specific proteinase (caspase) family proteins (Li et al., 2015; Ye et al., 2016). The Bcl‐2 family includes the antiapoptosis protein, bcl‐2, and the proapoptosis protein, bax.…”

Preventive Effect of YGDEY from Tilapia Fish Skin Gelatin Hydrolysates against Alcohol-Induced Damage in HepG2 Cells through ROS-Mediated Signaling Pathways

“…Apoptosis, the major form of controlled cell death [ 47 ], is the gene-controlled ordered death of a cell autonomously to maintain the stability of the inner environment [ 48 ]. Apoptosis is regulated by various molecules, such as the bcl-2 family proteins and the cysteinyl aspartate-specific proteinase (caspase) family [ 49 , 50 ]. The bcl-2 family can be classified into anti-apoptotic proteins (bcl-2 and bcl-x L ) and pro-apoptotic proteins (bax, bak, and bad) [ 51 ].…”