Anticancer mechanisms on pyroptosis induced by Oridonin: New potential targeted therapeutic strategies

作者：Guo Qiang Li, Shi Xiang Gao, Fu Han Wang, Kang Le, Ze Yao Tang, Dong Xiao · 发表于：Biomedicine & Pharmacotherapy · 年份：2023 · DOI：10.1016/j.biopha.2023.115019 · 被引用次数：19 · 研究领域：Inflammasome and immune disorders、Bioactive Natural Diterpenoids Research、Cell death mechanisms and regulation

Pyroptosis is a type of inflammatory cell death that is triggered by the formation of pores on the cell membrane by gasdermin (GSDM) family proteins. This process activates inflammasomes and leads to the maturation and release of proinflammatory cytokines such as interleukin-1β (IL-1β) and interleukin-18 (IL-18). Pyroptosis, a form of programmed cell death, has been found to be associated with various biomolecules such as caspases, granzymes, non-coding RNA (lncRNA), reactive oxygen species (ROS), and NOD-like receptor protein 3 (NLRP3). These biomolecules have been shown to play a dual role in cancer by affecting cell proliferation, metastasis, and the tumor microenvironment (TME), resulting in both tumor promotion and anti-tumor effects. Recent studies have found that Oridonin (Ori) has anti-tumor effects by regulating pyroptosis through various pathways. Ori can inhibit pyroptosis by inhibiting caspase-1, which is responsible for activating pyroptosis of the canonical pathway. Additionally, Ori can inhibit pyroptosis by inhibiting NLRP3, which is responsible for activating pyroptosis of the noncanonical pathway. Interestingly, Ori can also activate pyroptosis by activating caspase-3 and caspase-8, which are responsible for activating pyroptosis of the emerging pathway; Ori has been found to be effective in inhibiting pyroptosis by blocking the action of perforin, which is responsible for facilitating the entry of granzyme into cells and activating pyroptosis. Additionally,...