Omega-3 docosahexaenoic acid induces pyroptosis cell death in triple-negative breast cancer cells

Pizato, Nathalia; Luzete, Beatriz Christina; Kiffer, Larissa Fernanda Melo Vasconcelos; Corrêa, Luís Henrique; Santos, Igor de Oliveira; Assumpção, José Antônio Fagundes; Ito, Marina; Magalhães, Kelly Grace

doi:10.1038/s41598-018-20422-0

Cited by 176 publications

(141 citation statements)

References 66 publications

(75 reference statements)

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“…To date, many natural products from traditional Chinese medicines (TCMs) have been identified to have a potent anti-tumor effect [28,53]. TTM, a traditional Chinese medicine, was found to significantly suppress the proliferation of cancer cells and growth of tumors.…”

Section: Discussionmentioning

confidence: 99%

Polyphyllin VI Induces Caspase-1-Mediated Pyroptosis via the Induction of ROS/NF-κB/NLRP3/GSDMD Signal Axis in Non-Small Cell Lung Cancer

Teng

Mei

Zhou

et al. 2020

Cancers

231

146

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Trillium tschonoskii Maxim (TTM), a traditional Chinese medicine, has been demonstrated to have a potent anti-tumor effect. Recently, polyphyllin VI (PPVI), a main saponin isolated from TTM, was reported by us to significantly suppress the proliferation of non-small cell lung cancer (NSCLC) via the induction of apoptosis and autophagy in vitro and in vivo. In this study, we further found that the NLRP3 inflammasome was activated in PPVI administrated A549-bearing athymic nude mice. As is known to us, pyroptosis is an inflammatory form of caspase-1-dependent programmed cell death that plays an important role in cancer. By using A549 and H1299 cells, the in vitro effect and action mechanism by which PPVI induces activation of the NLRP3 inflammasome in NSCLC were investigated. The anti-proliferative effect of PPVI in A549 and H1299 cells was firstly measured and validated by MTT assay. The activation of the NLRP3 inflammasome was detected by using Hoechst33324/PI staining, flow cytometry analysis and real-time live cell imaging methods. We found that PPVI significantly increased the percentage of cells with PI signal in A549 and H1299, and the dynamic change in cell morphology and the process of cell death of A549 cells indicated that PPVI induced an apoptosis-to-pyroptosis switch, and, ultimately, lytic cell death. In addition, belnacasan (VX-765), an inhibitor of caspase-1, could remarkably decrease the pyroptotic cell death of PPVI-treated A549 and H1299 cells. Moreover, by detecting the expression of NLRP3, ASC, caspase-1, IL-1β, IL-18 and GSDMD in A549 and h1299 cells using Western blotting, immunofluorescence imaging and flow cytometric analysis, measuring the caspase-1 activity using colorimetric assay, and quantifying the cytokines level of IL-1β and IL-18 using ELISA, the NLRP3 inflammasome was found to be activated in a dose manner, while VX-765 and necrosulfonamide (NSA), an inhibitor of GSDMD, could inhibit PPVI-induced activation of the NLRP3 inflammasome. Furthermore, the mechanism study found that PPVI could activate the NF-κB signaling pathway via increasing reactive oxygen Cancers 2020, 12, 193 2 of 27 species (ROS) levels in A549 and H1299 cells, and N-acetyl-L-cysteine (NAC), a scavenger of ROS, remarkably inhibited the cell death, and the activation of NF-κB and the NLRP3 inflammasome in PPVI-treated A549 and H1299 cells. Taken together, these data suggested that PPVI-induced, caspase-1-mediated pyroptosis via the induction of the ROS/NF-κB/NLRP3/GSDMD signal axis in NSCLC, which further clarified the mechanism of PPVI in the inhibition of NSCLC, and thereby provided a possibility for PPVI to serve as a novel therapeutic agent for NSCLC in the future.

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Section: Discussionmentioning

confidence: 99%

Polyphyllin VI Induces Caspase-1-Mediated Pyroptosis via the Induction of ROS/NF-κB/NLRP3/GSDMD Signal Axis in Non-Small Cell Lung Cancer

Teng

Mei

Zhou

et al. 2020

Cancers

231

146

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“…Inflammasomes activation in response to a wide variety of endogenous or exogenous stimuli facilitates a programmed cell death, called pyroptosis via induction of caspase-1 activation. Therefore, inflammasomes have been reported to prevent cancer development and activation of inflammasomes was attributed to a mechanism for the anticancer agents, such as induction of pyroptosis by omega-3 docosahexaenoic acid in triple-negative breast cancer cells [27] and inhibition of hepatocellular carcinoma cell growth by estradiol [40]. However, in contrast to this notion, there has been an increasing appreciation that excessive inflammasomes activation could contribute to growth of the multiple types of cancer cells [18,19,22].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, activation of the inflammasome facilitates tumor progression [23,24], suggesting that inflammasomes act as mediators that bridge chronic inflammation and tumorigenesis. Interestingly, in contrast to this notion, it has been also well documented that the suppressive effects on tumor growth by various anticancer agents are mediated through inflammasomes activation, which initiates pyroptotic cell death in cancer cells [25][26][27]. These conflicting reports suggest that the outcome of inflammasomes activation in growth of cancer cells would be specific for cell type, tumor tissue, and the nature of the inducers or inhibitors.…”

Section: Introductionmentioning

confidence: 99%

Globular Adiponectin Inhibits Breast Cancer Cell Growth through Modulation of Inflammasome Activation: Critical Role of Sestrin2 and AMPK Signaling

Pham

Raut

Pandit

et al. 2020

Cancers

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Adiponectin, an adipokine predominantly derived from adipose tissue, exhibits potent antitumor properties in breast cancer cells. However, its mechanisms of action remain elusive. Inflammasomes—intracellular multimeric protein complexes—modulate cancer cell growth in a complicated manner, as well as playing a role in the innate immune system. Herein, we examined the potential role of inflammasomes in the antitumor activity of adiponectin and found that globular adiponectin (gAcrp) significantly suppressed inflammasomes activation in breast cancer cells both in vitro and in vivo conditions, as determined by decreased expression of inflammasomes components, including NOD-like receptor pyrin domain-containing protein 3 (NLRP3) and the apoptosis-associated speck-like protein containing a CARD (ASC), and inhibition of interleukin-1β and caspase-1 activation. Treatment with pharmacological inhibitors of inflammasomes caused decrease in cell viability, apoptosis induction, and G0/G1 cell cycle arrest, suggesting that inflammasomes activation is implicated in the growth of breast cancer cells. In addition, treatment with gAcrp generated essentially similar results to those of inflammasomes inhibitors, further indicating that suppression of breast cancer cell growth by gAcrp is mediated via modulation of inflammasomes. Mechanistically, gAcrp suppressed inflammasomes activation through sestrin2 (SESN2) induction, liver kinase B1 (LKB-1)-dependent AMP-activated protein kinase (AMPK) phosphorylation, and alleviation of endoplasmic reticulum (ER) stress. Taken together, these results demonstrate that gAcrp inhibits growth of breast cancer cells by suppressing inflammasomes activation, at least in part, via SESN2 induction and AMPK activation-dependent mechanisms.

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“…It has been reported that MST1 interacts with ROS and plays critical roles in apoptosis, autophagy, and tumor suppression (39)(40)(41)(42). Recently, studies have also demonstrated that ROS induces pyroptosis and suppresses cancer progression (43,44). Thus, we first assess the levels of ROS on pyroptosis in PDAC cells.…”

Section: Mst1 Suppresses Proliferation Migration and Invasion Via Rmentioning

confidence: 99%

MST1 Suppresses Pancreatic Cancer Progression via ROS-Induced Pyroptosis

Cui

Zhou

Yang

et al. 2019

Molecular Cancer Research

104

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Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease, and its incidence is increasing annually. It is critical to reveal and delineate the molecular mechanism promoting PDAC development and progression. Mammalian STE20-like kinase 1 (MST1) is a proapoptotic cytoplasmic kinase and also one of the core components of the Hippo pathway. Here, we showed that MST1 expression was decreased in PDAC, and restored expression of MST1 promoted PDAC cell death and suppressed the proliferation, migration, invasion, and cell spheroid formation of PDAC via caspase-1-induced pyroptosis. Further studies demonstrated that pyroptosis induced by MST1 was independent of the Hippo pathway, but mediated by reactive oxygen species (ROS). And ROS scavenger N-acetyl-cysteine attenuated the activation of caspase-1 induced by MST1 and the effect of MST1 in PDAC cell death, proliferation, migration, and invasion. Collectively, our study demonstrated that MST1 suppressed the progression of PDAC cells at least partly through ROS-induced pyroptosis.Implications: In this study, we identified a new mechanism of MST1 in inhibiting PDAC development and progression and revealed that MST1 would be a potential prognostic and therapeutic target for PDAC.

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Omega-3 docosahexaenoic acid induces pyroptosis cell death in triple-negative breast cancer cells

Cited by 176 publications

References 66 publications

Polyphyllin VI Induces Caspase-1-Mediated Pyroptosis via the Induction of ROS/NF-κB/NLRP3/GSDMD Signal Axis in Non-Small Cell Lung Cancer

Polyphyllin VI Induces Caspase-1-Mediated Pyroptosis via the Induction of ROS/NF-κB/NLRP3/GSDMD Signal Axis in Non-Small Cell Lung Cancer

Globular Adiponectin Inhibits Breast Cancer Cell Growth through Modulation of Inflammasome Activation: Critical Role of Sestrin2 and AMPK Signaling

MST1 Suppresses Pancreatic Cancer Progression via ROS-Induced Pyroptosis

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