Myricetin activates the Caspase-3/GSDME pathway via ER stress induction of pyroptosis in lung cancer cells

Han, Jicheng; Cheng, Cheng; Zhang, Jinxin; Fang, Jinbo; Yao, Wei; Zhu, Yan; Xiu, Zhiru; Jin, Ningyi; Lu, Huijun; Xiao, Li; Li, Yiquan

doi:10.3389/fphar.2022.959938

Cited by 23 publications

(10 citation statements)

References 39 publications

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“…According to the GO analysis, ER stress response-associated gene expressions were the most enriched. ER stress is known to mediate different modes of cell death, including autophagy, apoptosis, ferroptosis, and pyroptosis [47,48]. We detected the expression of p-IRE1α and CHOP increased in CT-treated A549 cells.…”

Section: Discussionmentioning

confidence: 83%

Cholestane-3β,5α,6β-triol Induces Multiple Cell Death in A549 Cells via ER Stress and Autophagy Activation

Chen,

Zhang,

Cai

et al. 2024

Marine Drugs

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Cholestane-3β,5α,6β-triol (CT) and its analogues are abundant in natural sources and are reported to demonstrate cytotoxicity toward different kinds of tumor cells without a deep probe into their mechanism of action. CT is also one of the major metabolic oxysterols of cholesterol in mammals and is found to accumulate in various diseases. An extensive exploration of the biological roles of CT over the past few decades has established its identity as an apoptosis inducer. In this study, the effects of CT on A549 cell death were investigated through cell viability assays. A RNA-sequencing analysis and western blot of CT-treated A549 cells revealed the role of CT in inducing endoplasmic reticulum (ER) stress response and enhancing autophagy flux, suggesting a putative mechanism of CT-induced cell-death activation involving reactive oxygen species (ROS)-mediated ER stress and autophagy. It is reported for the first time that the upregulation of autophagy induced by CT can serve as a cellular cytotoxicity response in accelerating CT-induced cell death in A549 cells. This research provides evidence for the effect of CT as an oxysterol in cell response to oxidative damage and allows for a deep understanding of cholesterol in its response in an oxidative stress environment that commonly occurs in the progression of various diseases.

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Section: Discussionmentioning

confidence: 83%

Cholestane-3β,5α,6β-triol Induces Multiple Cell Death in A549 Cells via ER Stress and Autophagy Activation

Chen,

Zhang,

Cai

et al. 2024

Marine Drugs

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“…Subsequent to the inhibition of caspase-12, there was a notable decrease in the expression levels of cleaved caspase-3 and cleaved GSDME. These results demonstrate that MYR induces lung cancer cell death mainly through pyroptosis induced by the ER stress pathway [ 127 ].…”

Section: Pyroptosismentioning

confidence: 95%

“…The results also demonstrated that GSDME and cleaved caspase-3 were significantly higher in the MYR-treated group compared to the untreated group. In summary, MYR may inhibit tumor growth and induce cell pyroptosis in vivo [ 127 ].…”

Section: Protective Effects Of Flavonoids Against Cancer: In Vivo Evi...mentioning

confidence: 99%

Selected Flavonols Targeting Cell Death Pathways in Cancer Therapy: The Latest Achievements in Research on Apoptosis, Autophagy, Necroptosis, Pyroptosis, Ferroptosis, and Cuproptosis

Wendlocha,

Kubina,

Krzykawski

et al. 2024

Nutrients

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The complex and multi-stage processes of carcinogenesis are accompanied by a number of phenomena related to the potential involvement of various chemopreventive factors, which include, among others, compounds of natural origin such as flavonols. The use of flavonols is not only promising but also a recognized strategy for cancer treatment. The chemopreventive impact of flavonols on cancer arises from their ability to act as antioxidants, impede proliferation, promote cell death, inhibit angiogenesis, and regulate the immune system through involvement in diverse forms of cellular death. So far, the molecular mechanisms underlying the regulation of apoptosis, autophagy, necroptosis, pyroptosis, ferroptosis, and cuproptosis occurring with the participation of flavonols have remained incompletely elucidated, and the results of the studies carried out so far are ambiguous. For this reason, one of the therapeutic goals is to initiate the death of altered cells through the use of quercetin, kaempferol, myricetin, isorhamnetin, galangin, fisetin, and morin. This article offers an extensive overview of recent research on these compounds, focusing particularly on their role in combating cancer and elucidating the molecular mechanisms governing apoptosis, autophagy, necroptosis, pyroptosis, ferroptosis, and cuproptosis. Assessment of the mechanisms underlying the anticancer effects of compounds in therapy targeting various types of cell death pathways may prove useful in developing new therapeutic regimens and counteracting resistance to previously used treatments.

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“…Transmission electron microscopy also revealed the existence of multiple pores, another hallmark of pyroptosis, with in cell membranes of myricetin-treated A549 cells and NCI-H446. When considered as a whole, the results show that myricetin causes pyroptosis in NCI-H446 and A549 cells by cleaving GSDME rather than GSDMD [103]. Cytotoxic potential of myricetin in A549 as well as A549-IR cells were examined.…”

Section: Lung Cancermentioning

confidence: 98%

Myricetin: A Significant Emphasis on Its Anticancer Potential via the Modulation of Inflammation and Signal Transduction Pathways

Rahmani

Almatroudi

Allemailem

et al. 2023

IJMS

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Cancer is a major public health concern worldwide and main burden of the healthcare system. Regrettably, most of the currently used cancer treatment approaches such as targeted therapy, chemotherapy, radiotherapy and surgery usually cause adverse complications including hair loss, bone density loss, vomiting, anemia and other complications. However, to overcome these limitations, there is an urgent need to search for the alternative anticancer drugs with better efficacy as well as less adverse complications. Based on the scientific evidences, it is proven that naturally occurring antioxidants present in medicinal plants or their bioactive compounds might constitute a good therapeutic approach in diseases management including cancer. In this regard, myricetin, a polyhydroxy flavonol found in a several types of plants and its role in diseases management as anti-oxidant, anti-inflammatory and hepato-protective has been documented. Moreover, its role in cancer prevention has been noticed through modulation of angiogenesis, inflammation, cell cycle arrest and induction of apoptosis. Furthermore, myricetin plays a significant role in cancer prevention through the inhibition of inflammatory markers such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (Cox-2). Moreover, myricetin increases the chemotherapeutic potential of other anticancer drugs through modulation of cell signaling molecules activity. This review elaborates the information of myricetin role in cancer management through modulating of various cell-signaling molecules based on in vivo and in vitro studies. In addition, synergistic effect with currently used anticancer drugs and approaches to improve bioavailability are described. The evidences collected in this review will help different researchers to comprehend the information about its safety aspects, effective dose for different cancers and implication in clinical trials. Moreover, different challenges need to be focused on engineering different nanoformulations of myricetin to overcome the poor bioavailability, loading capacity, targeted delivery and premature release of this compound. Furthermore, some more derivatives of myricetin need to be synthesized to check their anticancer potential.

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Myricetin activates the Caspase-3/GSDME pathway via ER stress induction of pyroptosis in lung cancer cells

Cited by 23 publications

References 39 publications

Cholestane-3β,5α,6β-triol Induces Multiple Cell Death in A549 Cells via ER Stress and Autophagy Activation

Cholestane-3β,5α,6β-triol Induces Multiple Cell Death in A549 Cells via ER Stress and Autophagy Activation

Selected Flavonols Targeting Cell Death Pathways in Cancer Therapy: The Latest Achievements in Research on Apoptosis, Autophagy, Necroptosis, Pyroptosis, Ferroptosis, and Cuproptosis

Myricetin: A Significant Emphasis on Its Anticancer Potential via the Modulation of Inflammation and Signal Transduction Pathways

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