Isobavachalcone’s Alleviation of Pyroptosis Contributes to Enhanced Apoptosis in Glioblastoma: Possible Involvement of NLRP3

Wu, Yueshan; Chang, Jing; Ge, Juanjuan; Xu, Kangyan; Zhou, Quan; Zhang, Xiaowen; Zhu, Ni; Hu, Meichun

doi:10.1007/s12035-022-03010-2

Cited by 12 publications

(6 citation statements)

References 56 publications

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“…We found that high‐dose IBC was as effective as doxorubicin and better tolerated. Consistent with our findings, previous studies have also demonstrated significant antitumor effects of IBC in vivo (Wu, Chang, et al, 2022; Xiao et al, 2023). There are relatively few clinical studies on IBC.…”

Section: Discussionsupporting

confidence: 93%

“…However, TM was not able to induce S-phase arrest despite increasing ROS production to a small extent. It Based on the intracellular effects of IBC and previous studies (Wu, Chang, et al, 2022;Wu, Gao, et al, 2022), we selected the doses of 10, 20, and 40 μM to investigate its mechanism of action, 30 and 60 mg/kg for the in vivo experiments. IBC inhibited xenograft growth by 25% and 53% at the low and high doses, respectively.…”

Section: Discussionmentioning

confidence: 99%

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Isobavachalcone, a natural sirtuin 2 inhibitor, exhibits anti‐triple‐negative breast cancer efficacy in vitro and in vivo

Ren,

Lei,

Zhang

et al. 2024

Phytotherapy Research

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Triple‐negative breast cancer (TNBC) is the most aggressive and lethal clinical subtype and lacks effective targeted therapies at present. Isobavachalcone (IBC), the main active component of Psoralea corylifolia L., has potential anticancer effects. Herein, we identified IBC as a natural sirtuin 2 (SIRT2) inhibitor and characterized the potential mechanisms underlying the inhibition of TNBC. Molecular dynamics analysis, enzyme activity assay, and cellular thermal shift assay were performed to evaluate the combination of IBC and SIRT2. The therapeutic effects, mechanism, and safety of IBC were analyzed in vitro and in vivo using cellular and xenograft models. IBC effectively inhibited SIRT2 enzyme activity with an IC50 value of 0.84 ± 0.22 μM by forming hydrogen bonds with VAL233 and ALA135 within its catalytic domain. In the cellular environment, IBC bound to and stabilized SIRT2, consequently inhibiting cellular proliferation and migration, and inducing apoptosis and cell cycle arrest by disrupting the SIRT2/α‐tubulin interaction and inhibiting the downstream Snail/MMP and STAT3/c‐Myc pathways. In the in vivo model, 30 mg/kg IBC markedly inhibited tumor growth by targeting the SIRT2/α‐tubulin interaction. Furthermore, IBC exerted its effects by inducing apoptosis in tumor tissues and was well‐tolerated. IBC alleviated TNBC by targeting SIRT2 and triggering the reactive oxygen species ROS/β‐catenin/CDK2 axis. It is a promising natural lead compound for future development of SIRT2‐targeting drugs.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Isobavachalcone, a natural sirtuin 2 inhibitor, exhibits anti‐triple‐negative breast cancer efficacy in vitro and in vivo

Ren,

Lei,

Zhang

et al. 2024

Phytotherapy Research

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“…It was also found that the inflammatory microenvironment was alleviated because of the inhibition of the NLRP3 inflammasome and the reduction of IL‐1β maturation 107 . In addition, the natural compound isbavachalone was also shown to further inhibit the proliferation, migration, and invasion of GBM cells by inhibiting the pyroptosis and inflammatory response associated with the NLRP3 inflammasome 108 …”

Section: Inhibition Of Pyroptosismentioning

confidence: 99%

Pyroptosis in glioma: Current management and future application

Guo,

Su,

Wei

et al. 2023

Immunological Reviews

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SummaryGlioma, the predominant form of central nervous system (CNS) malignancies, presents a significant challenge due to its high prevalence and low 5‐year survival rate. The efficacy of current treatment methods is limited by the presence of the blood–brain barrier, the immunosuppressive microenvironment, and other factors. Immunotherapy has emerged as a promising approach, as it can overcome the blood–brain barrier. A tumor's immune privilege, which is induced by an immunosuppressive environment, constricts immunotherapy's clinical impact in glioma. Pyroptosis, a programmed cell death mechanism facilitated by gasdermins, plays a significant role in the management of glioma. Its ability to initiate and regulate tumor occurrence, progression, and metastasis is well‐established. However, it is crucial to note that uncontrolled or excessive cell death can result in tissue damage, acute inflammation, and cytokine release syndrome, thereby potentially promoting tumor advancement or recurrence. This paper aims to elucidate the molecular pathways involved in pyroptosis and subsequently discuss its induction in cancer therapy. In addition, the current treatment methods of glioma and the use of pyroptosis in these treatments are introduced. It is hoped to provide more ideas for the treatment of glioma.

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“…For drug effects, the compound benzimidazoles can induce apoptosis and pyroptosis of human GBM cells by blocking the cell cycle ( 78 ), while the natural drug isobavitazarone (IBC). as a compound isolated from Psoralea corylifolia Linn seeds, can relieve pyroptosis and thus contribute to enhancing apoptosis of GBM cells ( 79 ). Moreover, IBC exerts an anti-cancer effect on leukemia, colorectal cancer, liver cancer, breast cancer, prostate cancer, stomach cancer, cervical cancer, ovarian cancer, tongue squamous cell carcinoma and myeloma.…”

Section: Natural Small-molecule Compounds Inhibit Glioma Through the ...mentioning

confidence: 99%

Regulated cell death in glioma: promising targets for natural small-molecule compounds

Han,

Li,

Fan

et al. 2024

Front. Oncol.

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Gliomas are prevalent malignant tumors in adults, which can be categorized as either localized or diffuse gliomas. Glioblastoma is the most aggressive and deadliest form of glioma. Currently, there is no complete cure, and the median survival time is less than one year. The main mechanism of regulated cell death involves organisms coordinating the elimination of damaged cells at risk of tumor transformation or cells hijacked by microorganisms for pathogen replication. This process includes apoptosis, necroptosis, autophagy, ferroptosis, pyroptosis, necrosis, parthanayosis, entosis, lysosome-dependent death, NETosis, oxiptosis, alkaliptosis, and disulfidaptosis. The main goal of clinical oncology is to develop therapies that promote the effective elimination of cancer cells by regulating cell death are the main goal of clinical oncology. Recently, scientists have utilized pertinent regulatory factors and natural small-molecule compounds to induce regulated cell death for the treatment of gliomas. By analyzing the PubMed and Web of Science databases, this paper reviews the research progress on the regulation of cell death and the role of natural small-molecule compounds in glioma. The aim is to provide help for the treatment of glioblastoma.

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Isobavachalcone’s Alleviation of Pyroptosis Contributes to Enhanced Apoptosis in Glioblastoma: Possible Involvement of NLRP3

Cited by 12 publications

References 56 publications

Isobavachalcone, a natural sirtuin 2 inhibitor, exhibits anti‐triple‐negative breast cancer efficacy in vitro and in vivo

Isobavachalcone, a natural sirtuin 2 inhibitor, exhibits anti‐triple‐negative breast cancer efficacy in vitro and in vivo

Pyroptosis in glioma: Current management and future application

Regulated cell death in glioma: promising targets for natural small-molecule compounds

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