Erianin induces GSDMD-dependent pyroptosis and synergistically enhances doxorubicin efficacy via the PI3K/AKT signaling pathway in Diffuse large B-cell lymphoma
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE271516 | GEO | 2026/07/01
REPOSITORIES: GEO
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Project description:Erianin, a natural product extracted from Dendrobium, possesses multiple pharmacological properties, including antioxidative and antitumor activities. The objective of this study was: to evaluate the anti-pancreatic cancer activity of erianin and explore its underlying mechanisms.To further explore the potential molecular mechanisms of erianin in pancreatic cancer, we performed RNA Sequencing analysis to identify DEGs under erianin stimulation in SW1990 cells.
2025-06-25 | GSE269714 | GEO
Project description:Anaplastic thyroid carcinoma (ATC) is an aggressive thyroid malignancy characterized by rapid progression, resistance to conventional therapies, and poor patient prognosis. There is an urgent need for innovative therapeutic strategies. Erianin, a natural compound derived from Dendrobium, has demonstrated significant anti-tumor effects in various cancers, yet its role in ATC remains unexplored.In this study, we confirmed the significant anticancer effects of erianin on ATC through both in vitro and in vivo models, including the induction of apoptosis and GSDME-dependent pyroptosis in ATC cells.
2025-09-24 | GSE299493 | GEO
Project description:Purpose: The precise temporal and spatial regulation of N5-methylcytosine (m5C) RNA modification plays essential roles in RNA metabolism. Targeting m5C regulation in cancer cells may be a potential strategy for cancer therapy. Erianin is a natural product isolated from Dendrobium chrysotoxum Lindl. Howbeit, the in‐depth understanding of interaction between erianin and m5C modification remains indistinct. Methods: Natural product library screening was used to explore the effects of natural product monomers on uveal melanoma (UM) cells. Intraocular xenografts model was established to examine the effect of erianin. Immunoprecipitation mass spectrometry (IP-MS) and molecular docking analyses were performed to identify NSUN2 as the target of erianin. m5C-meRIP-seq and m5C-meRIP-qPCR analyses were performed to identify the functional target of NSUN2. Tube formation assay and CD31-PAS double staining were used to detect vasculogenic mimicry (VM) in UM. Results: Herein, we report the discovery of erianin as an effective inhibitor of uveal melanoma. Mechanistically, the targeted inhibition of NSUN2 function by erianin results in a decrease in the m5C modification and expression levels of CHAC1 in UM, thereby curtailing the formation of VM. Conclusions: Collectively, our data suggested that erianin significantly inhibited UM progression in vitro and in vivo. Our study unveils a novel therapeutic strategy for combating UM.
2024-12-10 | GSE280936 | GEO
Project description:Erianin has been reported to play key roles in suppressing a wide variety of tumors. Howbeit, the mechanism underlying the erianin in anti-carcinogenesis remains to be fully addressed. Half-maximal inhibitory concentration (IC50) was detected to determine the influence of erianin on melanoma in vitro. Subcutaneous xenografts were established to observe the effect of erianin on the proliferation of melanoma cells in vivo. Transcriptome screening was performed to identify the meaningful target. Molecular docking and western blot were performed to verified the GSK3α-NF-κB cascade reaction. We reported the finding of Erianin as an efficient inhibitor of melanoma. Erianin selectively inhibited the growth of melanoma cells, rather than normal human melanocyte cell line. Specifically, erianin downregulated the cellular GSK3α-NF-κB pathway to induce melanoma cell apoptosis. Collectively, we initially proved that erianin inhibited melanoma effectively, which was caused by inactivation of GSK3α-NF-κB signaling inducing melanoma cells apoptosis. Thus, the study implies that erianin provides a novel therapeutic strategy for melanoma therapy.
2022-11-05 | GSE217070 | GEO
Project description:We studied transcriptional changes by Affymetrix human microarrays in DLBCL cell lines as a result of treatment with GSK126, a potent, highly-selective, SAM-competitive, small molecule inhibitor of EZH2 In eukaryotes, epigenetic post-translational modification of histones is critical for regulation of chromatin structure and gene expression. EZH2 is the catalytic subunit of the Polycomb Repressive Complex 2 (PRC2) and is responsible for repressing target gene expression through methylation of histone H3 on lysine 27 (H3K27). Over-expression of EZH2 is implicated in tumorigenesis and correlates with poor prognosis in multiple tumor types. Recent reports have identified somatic heterozygous mutations of Y641 and A677 residues within the catalytic SET domain of EZH2 in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). The Y641 residue is the most frequently mutated residue, with 22% of GCB (Germinal Cell B-cell) DLBCL and FL harboring mutations at this site. These lymphomas exhibit increased H3K27 tri-methylation (H3K27me3) due to altered substrate preferences of the mutant enzymes. However, it is unknown whether direct inhibition of EZH2 methyltransferase activity alone will be effective in treating lymphomas carrying activating EZH2 mutations. Herein, we demonstrate that GSK126, a potent, highly-selective, SAM-competitive, small molecule inhibitor of EZH2 methyltransferase activity, decreases global H3K27me3 levels and reactivates silenced PRC2 target genes. GSK126 effectively inhibits the proliferation of EZH2 mutant DLBCL cell lines and dramatically inhibits the growth of EZH2 mutant DLBCL xenografts in mice. Together, these data demonstrate that pharmacological inhibition of EZH2 activity may provide a promising treatment for EZH2 mutant lymphoma. 10 DLBCL cell lines (7 mutant and 3 wild type EZH2), that were differentially sensitive to GSK126 in proliferation assays, were treated for 72 hours, in duplicate (n=2), with either DMSO (vehicle) or 500nM of GSK126, a potent selective EZH2 inhibitor. EZH2 mutant cell lines are Pfeiffer, KARPAS-422, WSU-DLCL2, SU-DHL-10, SU-DHL-6, DB and SU-DHL-4. EZH2 wildtype cell lines are HT, OCI-LY-19 and Toledo.
2012-10-12 | E-GEOD-40971 | biostudies-arrayexpress
Project description:Erianin induces GSDMD-dependent pyroptosis and synergistically enhances doxorubicin efficacy via the PI3K/AKT signaling pathway in Diffuse large B-cell lymphoma
| PRJNA1132150 | ENA
Project description:CC-122 is a next-generation cereblon E3 ligase modulating agent that has demonstrated promising clinical efficacy in relapsed or refractory diffuse large B‐cell lymphoma (R/R DLBCL) patients. Mechanistically, CC-122 induces the degradation of IKZF1/3, leading to T cell activation and robust cell-autonomous killing in DLBCL. Here, we report a genome-wide CRISPR/Cas9 positive selection screen for CC-122 in a DLBCL cell line SU-DHL-4 with follow-up mechanistic characterization in 6 DLBCL cell lines to identify genes regulating the response to CC-122. Top-ranked CC-122 resistance genes encode not only well-defined members or regulators of the CUL4-DDB1-RBX1-CRBN E3 ubiquitin ligase complex, but also key components of several signaling and transcriptional networks that have not previously been shown to modulate the response to other cereblon modulators. Ablation of CYLD, NFKBIA, TRAF2, or TRAF3 induces hyper-activation of the canonical and/or non-canonical NF-κB pathways and subsequently diminishes CC-122-induced apoptosis in 5 out of 6 DLBCL cell lines. Depletion of KCTD5, the substrate receptor of the CUL3-RBX1-KCTD5 ubiquitin ligase complex, promotes the stabilization of its cognate substrate, GNG5, resulting in CC-122 resistance in HT, SU-DHL-4, and WSU-DLCL2. Furthermore, knockout of AMBRA1 renders resistance to CC-122 in SU-DHL-4 and U-2932, whereas knockout of RFX7 leads to resistance specifically in SU-DHL-4. The ubiquitous and cell line-specific mechanisms of CC-122 resistance in DLBCL cell lines revealed in this work pinpoint genetic alternations that are potentially associated with clinical resistance in patients, and facilitate the development of biomarker strategies for patient stratification, which may improve clinical outcome of CC-122 for R/R DLBCL.
2020-10-01 | GSE158303 | GEO
Project description:Background: Bromodomain and extra-terminal domain (BET) proteins and the spleen tyrosine kinase (SYK) represent promising targets in Diffuse large B-cell (DLBCL) and Burkitt’s lymphoma (BL). We evaluated the anti-lymphoma activity of the isoform specific bivalent BET inhibitor AZD5153 (AZD) and the pan-BET inhibitor I-BET151 (I-BET) as single agents and in combination with SYK inhibitor Entospletinib in vitro. Methods: Single agent exposures were evaluated on two DLBCL and two BL cell lines analyzing cell proliferation and metabolic activity. Proliferation, metabolic activity, apoptosis, cell cycle and morphology were investigated after combined AZD or I-BET and Ento exposure. RNAseq of combined AZD+Ento exposure was characterized in SU-DHL-4. Background: Bromodomain and extra-terminal domain (BET) proteins and the spleen tyrosine kinase (SYK) represent promising targets in Diffuse large B-cell (DLBCL) and Burkitt’s lymphoma (BL). We evaluated the anti-lymphoma activity of the isoform specific bivalent BET inhibitor AZD5153 (AZD) and the pan-BET inhibitor I-BET151 (I-BET) as single agents and in combination with SYK inhibitor Entospletinib in vitro. Methods: Single agent exposures were evaluated on two DLBCL and two BL cell lines analyzing cell proliferation and metabolic activity. Proliferation, metabolic activity, apoptosis, cell cycle and morphology were investigated after combined AZD or I-BET and Ento exposure. RNAseq of combined AZD+Ento exposure was characterized in SU-DHL-4. Results: Both BET inhibitors reduced cell proliferation/metabolic activity dose and time de-pendently. Combined BET and SYK inhibition enhanced the anti-proliferative effect and induc-ing a G0/G1 cell cycle arrest. SU-DHL-4 demonstrated a pronounced modulation of gene expres-sion by AZD, which was markedly increased by additional SYK inhibition. Functional enrich-ment analyses identified combination-specific GO terms related to cell division, transport and DNA replication. Genes such as PLEKHH3, MYB, SLC8A1, PARP9, HSPB1 and S100A4 were iden-tified as the presumable key regulators. Conclusion: Simultaneous inhibition of BET and SYK enhanced the anti-proliferative effects, and especially the combination-specific gene expression signature.
2022-07-08 | GSE207381 | GEO
Project description:Double Hit Lymphoma (DHL) were treated with the BRD4 inhibitor 100 nM CPI203 for 6h We used microarrays to uncover the mechanisms underlying CPI203 activity in Double Hit Lymphoma (DHL)
2017-11-01 | GSE98905 | GEO
Project description:Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphomas worldwide and is characterized by a high diversity of genetic and molecular alterations. Chromosomal translocations and mutations leading to deregulated expression of the transcriptional repressor BCL6 occur in a significant fraction of DLBCL patients. An oncogenic role of BCL6 in the initiation of DLBCL has been shown as the constitutive expression of BCL6 in mice recapitulates the pathogenesis of human DLBCL. However, the role of BCL6 in tumor maintenance remains poorly investigated due to the absence of suitable genetic models and limitations of pharmacological inhibitors. Here, we have utilized tetracycline-inducible CRISPR/Cas9 mutagenesis to study the consequences of BCL6 deletion in established DLBCL models in culture and in vivo. We show that BCL6 knock-out in SU-DHL-4 cells in vitro results in an anti-proliferative response 4-7 days after Cas9 induction that was characterized by cell cycle (G1) arrest. Conditional BCL6 deletion in established DLBCL tumors in vivo induced a significant tumor growth inhibition with initial tumor stasis followed by slow tumor growth kinetics. Our findings support a role of BCL6 in the maintenance of lymphoma growth and showcase the utility of inducible CRISPR/Cas9 systems for probing oncogene addiction.
2020-03-23 | GSE127266 | GEO