From gum inflammation to oral cancers: pyroptosis as the molecular torchbearer in periodontitis-driven carcinogenesis

Abstract

Periodontitis, a chronic inflammatory disease caused by bacterial infections in dental plaque, results in an environment rich in oxidative stress and pro-inflammatory cytokines, both of which contribute to oral cancers development. One critical mediator of inflammation in periodontitis is pyroptosis, a form of programmed cell death linked to inflammatory processes. Gasdermin D (GSDMD) is a key player in pyroptosis, where its cleavage forms membrane pores, leading to cell rupture and the release of pro-inflammatory cytokines like IL-1 beta and IL-18 creating an environment that favors cancer cell survival and proliferation. In periodontitis, pyroptosis is closely associated with the activation of inflammasomes, particularly NLRP3, in response to oral bacteria, which in turn leads to the release of cytokines that exacerbate inflammation. Furthermore, the tissue breakdown caused by pyroptosis releases damage-associated molecular patterns (DAMPs), which can activate oncogenic signaling in neighboring epithelial cells, further promoting oral cancers development. So, inhibiting pyroptotic mediators like GSDMD or NLRP3 inflammasomes can reduce inflammation in periodontitis and slow oral cancer progression. Interestingly, inducing pyroptosis in cancer cells or infected tissues may offer a potential therapeutic approach. These findings underscore the critical link between periodontitis, pyroptosis, and oral cancer, suggesting that targeting these pathways may offer therapeutic potential for preventing or treating both diseases. This review aims to elucidate the role of pyroptosis in periodontitis, their impacts on oral cancers, and the potential therapeutic strategies to modulate this inflammatory cell death.