Surfactin from Bacillus subtilis induces apoptosis in human oral squamous cell carcinoma through ROS-regulated mitochondrial pathway

Abstract

Recently, ambient air particulate matter (PM) has been shown to increase the risk of oral cancer. The most common malignant tumor in the oral cavity is oral squamous cell carcinoma (OSCC). Recent studies have revealed that surfactin, a cyclic lipopeptide generated by Bacillus subtilis , has anti-inflammatory and anti-cancer properties. However, the exact anti-cancer effects of surfactin on human OSCC and underlying molecular mechanisms remain largely unknown. In the present study, we found that treatment of SCC4 and SCC25 cells (human OSCC cell lines) with surfactin reduced the viability of SCC4 and SCC25 cells by induction of apoptosis. Surfactin-induced apoptosis was associated with caspase activation and poly(ADP-ribose) polymerase (PARP) cleavage and was regulated by the mitochondrial pathway, exemplified by mitochondrial depolarization, mitochondrial-derived reactive oxidative species (ROS) production, cytochrome c release, up-regulation of Bad and Bax, and down-regulation of Bcl-2. Surfactin induced NADPH oxidase-dependent ROS generation, which appeared essential for the activation of the mitochondrial pathway. Surfactin-induced mitochondrial-derived ROS generation was associated with JNK1/2 activation. After treatment with surfactin, ROS caused JNK1/2-dependent cell death of SCC4 and SCC25 cells. Taken together, our findings suggest that surfactin induces mitochondria associated apoptosis of human OSCC cell lines, and surfactin may be a potential chemotherapeutic agent for future OSCC treatment.

Costunolide Induces Apoptosis via the Reactive Oxygen Species and Protein Kinase B Pathway in Oral Cancer Cells

“…Our findings showed that CTD induced significant ROS generation; however, pretreatment with NAC significantly rescued the CTD-associated cell proliferation and apoptosis, suggesting that CTD exerts apoptotic effects through ROS generation in oral cancer cells ( Figure 7 ). Previous studies have reported that the ROS/MAPK pathways participate in inducing apoptosis in oral carcinoma and renal cell cancer, respectively [ 45 , 46 ], and our findings are consistent with this report. These results suggested that CTD induced apoptotic changes through the activation of the ROS/JNK pathway.…”

Roles of Mitochondria in Oral Squamous Cell Carcinoma Therapy: Friend or Foe?

“…First, mtROS can influence many signaling pathways. For example, mtROS could activate JNK, which induces caspase activation and apoptosis in OSCC [ 90 ]; mtROS could also activate the AMP-activated protein kinase (AMPK) pathway and inhibit the STAT3 pathway, which results in the suppression of the growth and proliferation of OSCC cells [ 91 ]. Second, mtROS can damage DNA, causing cell death [ 74 , 92 ].…”

“…Undoubtedly, ctROS also has this function. For example, ctROS damaged the MMP and induced the production of mtROS, which activated JNK and led to caspase activation in OSCC [ 90 ]. In addition, ctROS could cause the mPTP to open, after which MAP occurred in OSCC [ 97 ].…”

Antimicrobial Peptides Mediate Apoptosis by Changing Mitochondrial Membrane Permeability

“…Through the investigation of the mechanism of action of different AMPs, it was found that some AMPs cause damage to mitochondria when exercising their biological functions [ 12 , 13 , 14 ]. Mitochondria is a site for energy production in cells, playing an important role in regulating cell growth and death [ 15 ].…”