NLRP3 Inflammasome Inhibitor BAY-117082 Reduces Oral Squamous Cell Carcinoma Progression

Abstract

Oral cancer is one of the most common human malignancies, and its incidence is increasing worldwide. In particular, oral squamous cell carcinoma (OSCC) is characterized by high rates of proliferation, invasiveness, and metastasis. Currently, standard treatment for OSCC includes surgical removal, chemotherapy, and radiotherapy; however, the survival rate of patients with OSCC remains low, thus new therapies are needed. It has been proven that excessive NLRP3 inflammasome activation and apoptosis alteration may contribute to oral cancer progression. This study aimed to investigate the effect of BAY-117082, an NLRP3 inflammasome inhibitor, in an in vitro and in vivo xenograft model of oral cancer. In vitro results revealed that BAY-117082 at concentrations of 5, 10, and 30 µM was able to reduce OSCC cell viability. BAY-117082 at higher concentrations significantly reduced NLRP3, ASC, caspase-1, IL-1β, and IL-18 expression. Moreover, Bax, Bad, and p53 expression were increased, whereas Bcl-2 expression was reduced. Furthermore, the in vivo study demonstrated that BAY-117082 at doses of 2.5 and 5 mg/kg significantly decreased subcutaneous tumor mass, and also reduced NLRP3 inflammasome pathway activation. Therefore, based on these results, the use of BAY-117082 could be considered a promising strategy to counteract oral cancer progression, thanks its ability to modulate the NLRP3 inflammasome and apoptosis pathways.

Therapeutic Potential of BAY-117082, a Selective NLRP3 Inflammasome Inhibitor, on Metastatic Evolution in Human Oral Squamous Cell Carcinoma (OSCC)

“…The involvement of inflammasome in bladder cancer [13], gastric cancer [14], and leukemia [15] has been highlighted by several studies; however, the role of NLRP3 in DM due to OSCC has not been fully elucidated. Scientific evidence has shown that BAY 11-7082, a powerful inhibitor of the NLRP3 inflammasome [16], possesses various pharmacological abilities; it is also able to modulate the apoptosis process [17]. The purpose of this study was to evaluate the effect of BAY-117082, a selective NLRP3 inflammasome inhibitor, in an in vivo orthotopic model of OSCC and its role in the invasiveness and metastasis processes in neighbor organs such as lymph nodes, lung, and spleen tissues.…”

Molecular Mechanisms in Pathophysiology of Mucopolysaccharidosis and Prospects for Innovative Therapy

“…It can also inhibit NLRP3 inflammasome independently of NF-κB [376]. Its efficacy has been demonstrated in several animal models [377][378][379][380]. Due to its small molecular weight (207.25 Da), this molecule can easily cross the BBB [381], making it attractive for alleviating CNS symptoms of MPS.…”

NF-κB and its crosstalk with endoplasmic reticulum stress in atherosclerosis

“…In addition, BAY also suppresses the translocation and activation of AP-1, interferon regulatory factor-3 (IRF-3), and signal transducer and activator of transcription-1 (STAT-1) by inhibiting the phosphorylation or activation of ERK, p38, and JAK-2 ( 192 ). BAY is also an inhibitor of NLRP3 inflammasome and a modulator of apoptosis pathways shown in the management of psoriasis-like dermatitis and oral cancer ( 193 , 194 ). These suggest that BAY could serve as a lead compound in developing potent anti-inflammatory drugs with multiple targets in inflammatory responses.…”