Atractylenolide I enhances responsiveness to immune checkpoint blockade therapy by activating tumor antigen presentation

Xu, Hanchen; Jeught, Kevin Van der; Zhou, Zhuolong; Zhang, Lu; Yu, Tao; Sun, Yifan; Li, Yujing; Wan, Chunli; So, Kyeong A; Liu, Degang; Frieden, Michael; Fang, Yunzhang; Mosley, Amber L.; He, Xiaoming; Zhang, Xinna; Sandusky, George E.; Liu, Yunlong; Meroueh, Samy O.; Zhang, Chi; Wijeratne, Aruna B.; Huang, Cheng; Ji, Guang; Lu, Xiongbin

doi:10.1172/jci146832

Cited by 111 publications

(49 citation statements)

References 42 publications

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“…These results indicate that the inhibition of PSMD4 expression can promote carboplatin-induced EOC cell apoptosis and increase the carboplatin sensitivity of EOC cells. The positive effect of the PSMD4 in improving the chemotherapy sensitivity of EOC patients has been confirmed in some studies (12,25,26). What's more, one study has found that the antiangiogenic drug cediranib can directly inhibit or inhibit the expression of the PSMD4 gene by inducing hypoxia, and then down-regulate the homologous DNA repair of tumor cells, thereby acting as a DNA repair inhibitor to enhance the sensitivity of chemotherapy drugs (10).…”

Section: Discussionmentioning

confidence: 87%

Down-regulation of PSMD4 can attenuate autophagy, enhance the accumulation of intracellular ROS, and increase the sensitivity of epithelial ovarian cancer to carboplatin by inhibiting the NF-κB pathway

Li¹,

Zhou²,

Shen³

et al. 2021

Transl Cancer Res TCR

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Background: The incidence of ovarian cancer ranks third among female gynecological cancers in the world, and more than 90% of patients are epithelial ovarian cancer (EOC). Carboplatin is the first-line chemotherapy drug for the treatment of EOC patients. However, patients who are resistant to carboplatin often do not benefit from it. Therefore, finding a key molecule that affects carboplatin sensitivity is expected to enhance the efficacy of carboplatin in EOC treatment. Methods:The human EOC cell line SK-OV-3 and TOV-21G were used in this study. The secondgeneration sequencing technology was used to sequence the transcripts of carboplatin-resistant EOC cells and parental EOC cells. The bioinformatic analysis of the differentially expressed genes was performed by Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis.The EOC tissue chip in the Gene Expression Omnibus (GEO) database was also analyzed to screen the target gene. Flow cytometry, Hoechst staining, Western blot, MTS, mitochondrial specific reducing agent (Mito Tempo), and nuclear factor kappa-B (NF-κB) pathway inhibitor (BAY 11-7082) were used to explore the effect of proteasome 26S subunit, non-ATPase 4 (PSMD4) on the autophagy, apoptosis, and reactive oxygen species (ROS) accumulation of carboplatin-resistant EOC cells treated with carboplatin. In vivo, the carboplatin-resistant EOC cell lines treated with PSMD4 knockdown were injected subcutaneously into mice (twelve female BALB/c nude mice) to construct EOC subcutaneous xenograft tumor models.Results: Based on second-generation sequencing technology and bioinformatics analysis, it was found that PSMD4 is the core molecule in the carboplatin resistance regulatory network in EOC, and its expression is up-regulated in EOC carboplatin-resistant tissues and cells. In vitro and in vivo experimental results show that the down-regulated expression of PSMD4 is closely related to the increase in sensitivity of EOC to carboplatin. Mechanically, we found that inhibiting PSMD4 expression may inhibit the activation of the NF-κB pathway, promote carboplatin-induced ROS accumulation in EOC cells, inhibit EOC cell autophagy, and enhance the sensitivity of EOC to carboplatin.

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Section: Discussionmentioning

confidence: 87%

Down-regulation of PSMD4 can attenuate autophagy, enhance the accumulation of intracellular ROS, and increase the sensitivity of epithelial ovarian cancer to carboplatin by inhibiting the NF-κB pathway

Li¹,

Zhou²,

Shen³

et al. 2021

Transl Cancer Res TCR

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“…Camptothecin, curcumin (Rowaiye et al, 2021), isoquinoline alkaloids of Chelidonium majus (Noureini et al, 2017), amentoflavone (Revikumar, 2021), and emodin (Liu et al, 2019), are effective telomerase inhibitors. Some natural compounds, such as fucoidan (Yang et al, 2021), myricetin (Ghassemi-Rad et al, 2018, bergapten (Xie et al, 2018), and atractylenolide I (Xu et al, 2021), have good immunomodulatory effects so that they have great potential as candidates for immunotherapy in the future. In addition, tanshinone IIA analog , kolaflavanone (KLF) (Alrazi et al, 2021), eugenol (Abdalla et al, 2020), and millepachine (Yan F et al, 2021), considered as potentially potent microtubule inhibitors, inhibit cell growth by interfering with the formation of microtubules.…”

Section: Discussionmentioning

confidence: 99%

Research Status and Hotspots of Anticancer Natural Products Based on the Patent Literature and Scientific Articles

Shen

2022

Front. Pharmacol.

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Background: The patent literature contains a large amount of information on the internal state of current industrial technologies that are not available in other literature studies. Scientific articles are the direct achievements of theoretical research in this field and can reveal how current theories in basic research have developed. In this study, the progress and status of natural anticancer products in this field were summarized, and the research hotspots were explored through the analysis of the relevant patent literature and scientific articles.Methods: Patent data were retrieved from the incoPat patent retrieval database, and paper data were retrieved from the Web of Science core set and PubMed. GraphPad Prism 8, Microsoft Excel 2010, and CiteSpace 5.8.R3 were used to perform visual processing. The analyzed patent literature includes the patent applicant type, country (or region), and technical subject. The analyzed scientific article includes academic groups, subject areas, keyword clustering, and burst detection.Results: A total of 20,435 patent families and 38,746 articles were collected by 4 January 2022. At present, antitumor drugs derived from natural products mainly include 1) apoptosis inducers such as curcumin, gallic acid, resveratrol, Theranekron D6, and gaillardin; 2) topoisomerase inhibitors such as camptothecins, scaffold-hopped flavones, podophyllotoxin, oxocrebanine, and evodiamine derivatives; 3) telomerase inhibitors such as camptothecin and isoquinoline alkaloids of Chelidonium majus, amentoflavone, and emodin; 4) microtubule inhibitors such as kolaflavanone, tanshinone IIA analog, eugenol, and millepachine; 5) immunomodulators such as fucoidan, myricetin, bergapten, and atractylenolide I; 6) tumor microenvironment regulators such as beta-escin and icaritin; 7) multidrug resistance reversal agents such as berberine, quercetin, and dihydromyricetin; and 8) antiangiogenic and antimetastatic agents such as epigallocatechin-3-gallate, lupeol, ononin, and saikosaponin A.Conclusion: Anticancer natural product technology was introduced earlier, but the later development momentum was insufficient. In addition, scientific research activities are relatively closed, and technical exchanges need to be strengthened. Currently, the development of medicinal plants and the research on the anticancer mechanism of natural active products are still research hotspots, especially those related to immune checkpoints, essential oils, and metastatic cancer. Theories of traditional Chinese medicine (TCM), such as “restraining excessiveness to acquire harmony,” “same treatment for different diseases,” “Meridian induction theory,” and “Fuzheng Quxie,” have important guiding significance to the research of anticancer mechanisms and the development of new drugs and can provide new ideas for this process.Systematic Review Registration: [https://sourceforge.net/projects/citespace/], identifier [000755430500001].

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“…For example, the study of Jiang et al. showed that PSMD4 can regulate the level of hypoxia-inducible factor 1α through the PTEN/Akt signaling pathway, thereby promoting the occurrence of hepatocellular carcinoma ( Jiang et al., 2019 ); PSMD4 can inhibit endoplasmic reticulum (ER) stress–induced cells apoptosis, advertising the development of esophageal cancer ( Ma et al., 2019 ); in addition, Xu et al. (2021) showed that PSMD4 is a potential target in mouse colorectal cancer, mediating the enhancement of immunoproteasome activity by atractylenolide I (ATT-I), making the body more responsive to immune checkpoint blocking therapy.…”

Section: Discussionmentioning

confidence: 99%

Identification and Validation of Immune-Related Biomarker Gene and Construction of ceRNA Networks in Septic Cardiomyopathy

et al. 2022

Front. Cell. Infect. Microbiol.

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Septic cardiomyopathy (SCM) is a cardiac dysfunction caused by severe sepsis, which greatly increases the risk of heart failure and death, and its molecular mechanism is unclear. The immune response has been reported to be an important process in septic cardiomyopathy and is present in the cardiac tissue of patients with sepsis, suggesting that the immune response may be an underlying mechanism of myocardial injury in SCM. Therefore, we explored the role of immune-related genes (IRGs) in SCM and aimed to identify pivotal immune-related targets with the aim of identifying key immune-related targets in SCM and potential therapeutic mechanisms involved in the pathological process of SCM. To explore the regulatory mechanisms of immune responses in SCM, we identified differentially expressed genes (DEGs) shared in the SCM datasets GSE179554 and GSE40180 by bioinformatics analysis and then obtained hub genes from the DEGs. Then, we obtained the immune-related hub genes (IRHGs) by intersecting the hub genes with IRGs and performed quantitative reverse transcription polymerase chain reaction to confirm the abnormal expression of IRHGs. Finally, we further constructed an immune-related lncRNA–miRNA–IRHG ceRNA regulatory network. In this study, we identified an IRHG that may be involved in the pathogenesis of SCM, which helps us to further elucidate the role of immune response in SCM and gain insights into the molecular mechanisms and potential therapeutic targets of SCM.

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Atractylenolide I enhances responsiveness to immune checkpoint blockade therapy by activating tumor antigen presentation

Cited by 111 publications

References 42 publications

Down-regulation of PSMD4 can attenuate autophagy, enhance the accumulation of intracellular ROS, and increase the sensitivity of epithelial ovarian cancer to carboplatin by inhibiting the NF-κB pathway

Down-regulation of PSMD4 can attenuate autophagy, enhance the accumulation of intracellular ROS, and increase the sensitivity of epithelial ovarian cancer to carboplatin by inhibiting the NF-κB pathway

Research Status and Hotspots of Anticancer Natural Products Based on the Patent Literature and Scientific Articles

Identification and Validation of Immune-Related Biomarker Gene and Construction of ceRNA Networks in Septic Cardiomyopathy

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