Kaempferol-induced mitochondrial damage promotes NF-κB- NLRP3-caspase-1 signaling axis-mediated pyroptosis in gastric cancer cells

Abstract

Purpose：Gastric cancer （GC）is a gastrointestinal tumor with high morbidity and mortality. Owing to the high rate of postoperative recurrence associated with GC, the effectiveness of radiotherapy and chemotherapy may be compromised by the occurrence of severe undesirable side effects. In light of these circumstances, kaempferol (KP), a flavonoid abundantly present in diverse herbal and fruit sources, emerges as a promising therapeutic agent with inherent anti-tumor properties. This study endeavors to demonstrate the therapeutic potential of KP in the context of Gastric cancer while unraveling the intricate underlying mechanisms. Methods：We employed methods of bioinformatics, network pharmacology, and molecular docking, followed by multiple experimental validations. Result：Our investigations unveil that KP stimulation effectively promotes the activation of NLRP3 inflammatory vesicles within AGS cells by engaging the NF-κB signaling pathway. Consequently, the signal cascade triggers the cleavage of Caspase-1, culminating in the liberation of IL-18. Furthermore, we ascertain that KP facilitate AGS cell pyroptosis by inducing mitochondrial damage. Conclusion：Our findings showcase KP as a compelling candidate for the treatment of Gastric cancer -related diseases, heralding new possibilities for future therapeutic interventions.