α‐NETA induces pyroptosis of epithelial ovarian cancer cells through the GSDMD/caspase‐4 pathway

Qiao, Lianqiao; Wu, Xiaomei; Zhang, Jing; Liu, Lei; Sui, Xiaoxin; Zhang, Ru; Liu, Wenxue; Shen, Fei; Sun, Yunyan; Xi, Xiaowei

doi:10.1096/fj.201900483rr

Cited by 81 publications

(63 citation statements)

References 20 publications

(47 reference statements)

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“…Pyroptotic cell death is associated with key morphological changes including the swelling of cells, osmotic lysis, and plasma membrane rupture [ 20 ]. Pyroptosis activation requires ASC dependent caspase-1, a key protein in the cleavage and secretion of active IL-1β and IL-18.…”

Section: Resultsmentioning

confidence: 99%

Melatonin attenuates smoking-induced atherosclerosis by activating the Nrf2 pathway via NLRP3 inflammasomes in endothelial cells

Zhao

Wang

Zhang

et al. 2021

Aging

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Substantial evidence suggests that the effects of smoking in atherosclerosis are associated with inflammation mediated by endothelial cells. However, the mechanisms and potential drug therapies for smoking-induced atherosclerosis remain to be clarified. Considering that melatonin exerts beneficial effects in cardiovascular diseases, we examined its effects on cigarette smoke-induced vascular injury. We found that cigarette smoke extract (CSE) treatment induced NLRP3-related pyroptosis in human aortic endothelial cells (HAECs). CSE also induced ROS generation and upregulated the Nrf2 pathway in HAECs. Furthermore, pretreatment of HAECs with Nrf2-specific siRNA and an Nrf2 activator revealed that Nrf2 can inhibit CSE-induced ROS/NLRP3 activation. Nrf2 also improved cell viability and the expression of VEGF and eNOS in CSE-treated HAECs. In balloon-induced carotid artery injury model rats exposed to cigarette smoke, melatonin treatment reduced intimal hyperplasia in the carotid artery. Mechanistic studies revealed that compared with the control group, Nrf2 activation was increased in the melatonin group, whereas ROS levels and the NLRP3 inflammasome pathway were inhibited. These results reveal that melatonin might effectively protect against smoking-induced vascular injury and atherosclerosis through the Nrf2/ROS/NLRP3 signaling pathway. Overall, these observations provide compelling evidence for the clinical use of melatonin to reduce smoking-related inflammatory vascular injury and atherosclerosis.

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Section: Resultsmentioning

confidence: 99%

Melatonin attenuates smoking-induced atherosclerosis by activating the Nrf2 pathway via NLRP3 inflammasomes in endothelial cells

Zhao

Wang

Zhang

et al. 2021

Aging

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“…These results have also been confirmed in in vivo studies. Taken together, these findings suggest that induction of pyroptosis represents a new anticancer strategy for epithelial ovarian cancer therapy (62).…”

Section: Pyroptosis In Cancermentioning

confidence: 87%

Induction of Pyroptosis and Its Implications in Cancer Management

2019

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Pyroptosis is a gasdermins mediated programmed cell death, which has been widely studied in inflammatory disease models. Recently, there are growing evidences that pyroptosis can be chemically induced in cancer cells without any bacterial or viral infection. Pyroptosis may affect all stages of carcinogenesis and has become a new topic in cancer research. In this review, we first briefly introduced pyroptosis. In the subsequent section, we discussed the induction of pyroptosis in cancer and its potential role as a promising target for cancer therapy. In addition, the biological characteristics of gasdermin D (GSDMD) and gasdermin E (GSDME), two important pyroptosis substrates, and their prognostic role in cancer management were reviewed. These results help us to understand the pathogenesis of cancer and develop new drugs, which based on pyroptosis modulation, for cancer patients.

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“…As a critical form of cell death, pyroptosis has been reported to be involved in many physiological processes, such as regulation of tumor immune microenvironment [35], treatment of acute myeloid leukemia [36] and act as an innate immune effector against intracellular bacteria [37]. There are various researches showing an association between pyroptosis and tumor proliferation [38][39][40]. In this study, we found that tanshinone II A enhanced cell proliferation and inhibited apoptosis by up-regulating GSDMD expression on HeLa cells, especially at high concentrations.…”

Section: Discussionmentioning

confidence: 99%

Tanshinone II A enhances pyroptosis and represses cell proliferation of HeLa cells by regulating miR-145/GSDMD signaling pathway

2020

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Cervical cancer is the fourth most common cancer in women globally. Lack of effective pharmacotherapies for cervical cancer mainly attributed to an elusive understanding of the mechanism underlying its pathogenesis. Pyroptosis plays a key role in inflammation and cancer. Our study identified microRNA (miR) 145 (miR-145)/gasdermin D (GSDMD) signaling pathway as critical mediators in the effect of tanshinone II A on HeLa cells. In the present study, we found that treatment of tanshinone II A led to an obvious repression of cell proliferation and an increase in apoptosis on HeLa cells, especially in high concentration. Compared with the controlled group, tanshinone II A enhanced the activity of caspase3 and caspase9. Notably, the results demonstrated that tanshinone II A regulated cell proliferation of HeLa cells by regulating miR-145/GSDMD signaling pathway. Treatment of tanshinone II A significantly up-regulated the expression of GSDMD and miR-145. After transfection of si-miR-145 plasmids, the effects of tanshinone II A on HeLa cells were converted, including cell proliferation, apoptosis and pyroptosis. In addition, the results showed that tanshinone II A treatment altered the expression level of PI3K, p-Akt, NF-kB p65 and Lc3-I. Collectively, our findings demonstrate that tanshinone II A exerts anticancer activity on HeLa cells by regulating miR-145/GSDMD signaling. The present study is the first time to identify miR-145 as a candidate target in cervical cancer and show an association between miR-145 and pyroptosis, which provides a novel therapy for the treatment of cervical cancer.

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α‐NETA induces pyroptosis of epithelial ovarian cancer cells through the GSDMD/caspase‐4 pathway

Cited by 81 publications

References 20 publications

Melatonin attenuates smoking-induced atherosclerosis by activating the Nrf2 pathway via NLRP3 inflammasomes in endothelial cells

Melatonin attenuates smoking-induced atherosclerosis by activating the Nrf2 pathway via NLRP3 inflammasomes in endothelial cells

Induction of Pyroptosis and Its Implications in Cancer Management

Tanshinone II A enhances pyroptosis and represses cell proliferation of HeLa cells by regulating miR-145/GSDMD signaling pathway

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