<p>Ursolic Acid Protects Against Proliferation and Inflammatory Response in LPS-Treated Gastric Tumour Model and Cells by Inhibiting NLRP3 Inflammasome Activation</p>

Abstract

Background Inflammation is considered as one of the hallmarks of cancer development and progression. Ursolic acid (UA) showed strong effects as an anti-inflammatory and antioxidant. However, the anti-cancer effects of ursolic acid require further study. Methods This study aimed to investigate the role of ursolic acid in a lipopolysaccharide (LPS)-treated gastric tumour mouse model and in a human gastric carcinoma cell line (BGC-823 cells). This study also aimed to confirm whether ursolic acid can protect against proliferation and the inflammatory response induced by LPS, by inhibiting the activation of the NLRP3 inflammasome via the NF-κB pathway. Results The present study demonstrated that ursolic acid significantly attenuated LPS-treated proliferation in a gastric tumour mouse model and the human gastric carcinoma BGC-823 cell line, reduced the expression of the NLRP3 inflammasome and suppressed the release of pro-inflammatory cytokines. In addition, ursolic acid inhibited the LPS-induced activation of NF-κB. Furthermore, the NF-κB pathway regulated the activation of the NLRP3 inflammasome. Conclusion In conclusion, these results demonstrated that ursolic acid could suppress proliferation and the inflammatory response in an LPS-induced mouse gastric tumour model and human BGC-823 cells by inhibiting the activation of the NLRP3 inflammasome via the NF-κB pathway. This indicates that ursolic acid can be a potential therapeutic agent for the treatment of gastric cancer.

Golgi phosphoprotein 3 promotes the proliferation of gallbladder carcinoma cells via regulation of the NLRP3 inflammasome

“…Several studies have reported that the activation of the NLRP3/Caspase-1 pathway is associated with tumor progression (24)(25)(26)(27). Wang et al (25) found that when the NLRP3 inflammasome is activated, Caspase-1 is spliced to further activate the Akt, GSK-3p, ERK1/2 and CREB signaling pathways to promote tumor proliferation.…”

“…Physiological levels of NLRP3 activation protects the body's inflammatory immune system via activation of Caspase-1, whereas uncontrolled activation will lead to dysregulated inflammation, autoimmune diseases, neurodegenerative diseases, and even malignant tumors (20)(21)(22)(23)(24). Recently, a number of studies have reported that the overactivation of NLRP3 is closely associated with the progression of several malignant tumors (24)(25)(26)(27). To date, there are numerous studies on the downstream effects of NLRP3 (22)(23)(24)(25).…”

Ursolic acid silences CYP19A1/aromatase to suppress gastric cancer growth

“…The 5-FU treatment using a therapy relevant dosing 5 mg/kg, 31 where UA was treated in an toxicological acceptable dose 20 mg/ kg. 32 We found that UA exerted extraordinary efficacy (TSI = ~90%) compared to 5-FU (TSI = ~40%). The tumor weight and tumor weight/body weight (TW/BW) ratio were significantly reduced in the UA-treated mice compared to the placebo-treated mice and 5-FU-treated mice (Figure 4C).…”

“…Moreover, we compared the tumor suppression efficacy of 5‐FU and UA (Figure 4A,B) and evaluated their systemic toxicity (Figure 4C) in MKN45 cells xenografted to create a GCa in vivo model. The 5‐FU treatment using a therapy relevant dosing 5 mg/kg, 31 where UA was treated in an toxicological acceptable dose 20 mg/kg 32 . We found that UA exerted extraordinary efficacy (TSI = ~90%) compared to 5‐FU (TSI = ~40%).…”

“…1 × 10 7 of MKN45 cells were subcutaneous (s.c.) injected into two sites on the lower back of each mouse. When the tumor volume reached 200 mm 3 , the mice were randomly assigned to three groups (placebo, 5‐FU (5 mg/kg 31 ), and ursolic acid (20 mg/kg 32 )). The mice then received IP injections of the assigned treatment three times a week for a total of 4 weeks.…”