Mechanistic insights curcumin’s anti-inflammatory in pancreatic cancer: experimental and computational evidence implicating IL1B interference via IL10RA upregulation and NLRP3/TLR3 downregulation
PurposePancreatic cancer is a highly aggressive malignancy characterised by a complex tumour microenvironment and chronic inflammation. Studies found curcumin inhibited with inflammatory responses and tumour proliferation by interfering with production and activation of pro-inflammatory factors. Thi...
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Frontiers Media S.A.
2025-06-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2025.1601908/full |
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| author | Jun-Feng Cao Jun-Feng Cao Kuan Hang Hao Zhang Qingjie Xia Xiao Zhang Jie Men Jin Tian Zengliang Xia Dunshui Liao Kezhou Li Kezhou Li |
| author_facet | Jun-Feng Cao Jun-Feng Cao Kuan Hang Hao Zhang Qingjie Xia Xiao Zhang Jie Men Jin Tian Zengliang Xia Dunshui Liao Kezhou Li Kezhou Li |
| author_sort | Jun-Feng Cao |
| collection | DOAJ |
| description | PurposePancreatic cancer is a highly aggressive malignancy characterised by a complex tumour microenvironment and chronic inflammation. Studies found curcumin inhibited with inflammatory responses and tumour proliferation by interfering with production and activation of pro-inflammatory factors. This study investigated curcumin treated pancreatic cancer by modulating key targets in the inflammatory response and their signalling pathways.MethodsThe human pancreatic cancer PL45 cells and SUIT-2 cells were utilized to establish cellular experiments, and the effects of curcumin on proliferation, apoptosis and cell migration of PL45 cells and SUIT-2 cells were detected by CCK-8, Annexin V-FITC/PI and cell scratching experiment. PL45 cells RNA from experimental and control groups was also analyzed by transcriptome sequencing. Bioinformatics screening of differential gene targets in transcriptome sequencing was performed. Gene Ontology, KEGG and Protein-protein interaction were used to analyze the differentially expressed targets at the gene level and protein level, respectively. We validated the differential gene targets by machine learning analysis of GSE28735 data, and performed survival analysis, pan-tumor analysis, immune infiltration analysis and single-cell transcriptional analysis on the differentially expressed targets. Computer simulations were utilized to verify the stability of curcumin binding to key proteins.ResultsResults of cellular experiments suggested 30 μg/mL curcumin and 50 μg/mL curcumin significantly inhibited the proliferation and growth of PL45 and SUIT-2, respectively. The transcriptome results indicated that 2,676 genes showed differential expression in curcumin-treated group compared to control group. Bioinformatics and machine learning analyses screened 14 key targets that are closely related to the inflammatory response in pancreatic cancer. Molecular dynamics showed binding free energies for IL1B/Curcumin, IL10RA/Curcumin, NLRP3/Curcumin and TLR3/Curcumin were −12.76 ± 1.41 kcal/mol, −11.42 ± 2.57 kcal/mol, −28.16 ± 3.11 kcal/mol and −12.54 ± 4.80 kcal/mol, respectively.ConclusionThis research findings indicated that curcumin not only directly interfered with the activation of IL1B through blocking activation of NLRP3 by TLR3, but also upregulated expression of IL10RA to activate IL-10, thereby interfering with IL1B and its downstream signalling pathway. |
| format | Article |
| id | doaj-art-63462bc204fc423a8a5678cc303f360e |
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| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj-art-63462bc204fc423a8a5678cc303f360e2025-08-20T02:01:54ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2025-06-011310.3389/fcell.2025.16019081601908Mechanistic insights curcumin’s anti-inflammatory in pancreatic cancer: experimental and computational evidence implicating IL1B interference via IL10RA upregulation and NLRP3/TLR3 downregulationJun-Feng Cao0Jun-Feng Cao1Kuan Hang2Hao Zhang3Qingjie Xia4Xiao Zhang5Jie Men6Jin Tian7Zengliang Xia8Dunshui Liao9Kezhou Li10Kezhou Li11Division of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaCollege of Medicine, Southwest Jiaotong University, Chengdu, Sichuan, ChinaDivision of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaDivision of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaInstitute of Neurological Diseases, Translation Neuroscience Center, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaChengdu Medical College, Chengdu, Sichuan, ChinaCollege of Medicine, Southwest Jiaotong University, Chengdu, Sichuan, ChinaCollege of Medicine, Southwest Jiaotong University, Chengdu, Sichuan, ChinaInstitute of Neurological Diseases, Translation Neuroscience Center, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaInstitute of Neurological Diseases, Translation Neuroscience Center, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaDivision of Pancreatic Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, ChinaCollege of Medicine, Southwest Jiaotong University, Chengdu, Sichuan, ChinaPurposePancreatic cancer is a highly aggressive malignancy characterised by a complex tumour microenvironment and chronic inflammation. Studies found curcumin inhibited with inflammatory responses and tumour proliferation by interfering with production and activation of pro-inflammatory factors. This study investigated curcumin treated pancreatic cancer by modulating key targets in the inflammatory response and their signalling pathways.MethodsThe human pancreatic cancer PL45 cells and SUIT-2 cells were utilized to establish cellular experiments, and the effects of curcumin on proliferation, apoptosis and cell migration of PL45 cells and SUIT-2 cells were detected by CCK-8, Annexin V-FITC/PI and cell scratching experiment. PL45 cells RNA from experimental and control groups was also analyzed by transcriptome sequencing. Bioinformatics screening of differential gene targets in transcriptome sequencing was performed. Gene Ontology, KEGG and Protein-protein interaction were used to analyze the differentially expressed targets at the gene level and protein level, respectively. We validated the differential gene targets by machine learning analysis of GSE28735 data, and performed survival analysis, pan-tumor analysis, immune infiltration analysis and single-cell transcriptional analysis on the differentially expressed targets. Computer simulations were utilized to verify the stability of curcumin binding to key proteins.ResultsResults of cellular experiments suggested 30 μg/mL curcumin and 50 μg/mL curcumin significantly inhibited the proliferation and growth of PL45 and SUIT-2, respectively. The transcriptome results indicated that 2,676 genes showed differential expression in curcumin-treated group compared to control group. Bioinformatics and machine learning analyses screened 14 key targets that are closely related to the inflammatory response in pancreatic cancer. Molecular dynamics showed binding free energies for IL1B/Curcumin, IL10RA/Curcumin, NLRP3/Curcumin and TLR3/Curcumin were −12.76 ± 1.41 kcal/mol, −11.42 ± 2.57 kcal/mol, −28.16 ± 3.11 kcal/mol and −12.54 ± 4.80 kcal/mol, respectively.ConclusionThis research findings indicated that curcumin not only directly interfered with the activation of IL1B through blocking activation of NLRP3 by TLR3, but also upregulated expression of IL10RA to activate IL-10, thereby interfering with IL1B and its downstream signalling pathway.https://www.frontiersin.org/articles/10.3389/fcell.2025.1601908/fullcurcuminpancreatic cancermachine learningtranscriptome sequencingcellular experimentscomputer simulation |
| spellingShingle | Jun-Feng Cao Jun-Feng Cao Kuan Hang Hao Zhang Qingjie Xia Xiao Zhang Jie Men Jin Tian Zengliang Xia Dunshui Liao Kezhou Li Kezhou Li Mechanistic insights curcumin’s anti-inflammatory in pancreatic cancer: experimental and computational evidence implicating IL1B interference via IL10RA upregulation and NLRP3/TLR3 downregulation Frontiers in Cell and Developmental Biology curcumin pancreatic cancer machine learning transcriptome sequencing cellular experiments computer simulation |
| title | Mechanistic insights curcumin’s anti-inflammatory in pancreatic cancer: experimental and computational evidence implicating IL1B interference via IL10RA upregulation and NLRP3/TLR3 downregulation |
| title_full | Mechanistic insights curcumin’s anti-inflammatory in pancreatic cancer: experimental and computational evidence implicating IL1B interference via IL10RA upregulation and NLRP3/TLR3 downregulation |
| title_fullStr | Mechanistic insights curcumin’s anti-inflammatory in pancreatic cancer: experimental and computational evidence implicating IL1B interference via IL10RA upregulation and NLRP3/TLR3 downregulation |
| title_full_unstemmed | Mechanistic insights curcumin’s anti-inflammatory in pancreatic cancer: experimental and computational evidence implicating IL1B interference via IL10RA upregulation and NLRP3/TLR3 downregulation |
| title_short | Mechanistic insights curcumin’s anti-inflammatory in pancreatic cancer: experimental and computational evidence implicating IL1B interference via IL10RA upregulation and NLRP3/TLR3 downregulation |
| title_sort | mechanistic insights curcumin s anti inflammatory in pancreatic cancer experimental and computational evidence implicating il1b interference via il10ra upregulation and nlrp3 tlr3 downregulation |
| topic | curcumin pancreatic cancer machine learning transcriptome sequencing cellular experiments computer simulation |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2025.1601908/full |
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