Pub Date : 2026-02-04DOI: 10.1186/s11658-025-00851-2
Holger A Lindner, Carolina de la Torre, Sonia Y Velásquez, Jutta Schulte, Carsten Sticht, Manfred Thiel, Anna Coulibaly
{"title":"Sepsis alters NK cell transcriptional programs for stress, actin remodeling, and intracellular trafficking.","authors":"Holger A Lindner, Carolina de la Torre, Sonia Y Velásquez, Jutta Schulte, Carsten Sticht, Manfred Thiel, Anna Coulibaly","doi":"10.1186/s11658-025-00851-2","DOIUrl":"10.1186/s11658-025-00851-2","url":null,"abstract":"","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":" ","pages":""},"PeriodicalIF":10.2,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12954936/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146118076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-24DOI: 10.1186/s11658-025-00846-z
Yan Li, Bingqi Zhang, Zhongmin Zhang, Wei Yan, Haoyu Wang, Xun Xu, Anqi Lv, Zhengming Liao, Lang Guo
Background: Patients with castration-resistant prostate cancer (CRPC) often develop resistance following long-term enzalutamide treatment. Building upon previous research, we aims to further explore the effect of ilicicolin A (ili-A) on enzalutamide resistance and to elucidate the underlying resistance mechanisms.
Methods: Proliferation, migration, and invasion of prostate cancer (PCa) cells were evaluated by 5-ethynyl-2'-deoxyuridine (EdU) assays, colony formation, scratch, and Transwell. Cell Counting Kit 8 (CCK-8) was used to assess the efficacy of drug inhibition in CRPC cells. The expression of tumor cell apoptotic proteins and ferroptosis was assessed using western blot (WB) analysis. Coimmunoprecipitation (Co-IP) and proximity ligation assay (PLA) were used to identify the mechanism of interaction between ilicicolin A and ferroptosis. Tumor transplantation experiments with mice were conducted to confirm findings.
Results: Ili-A showed dose-dependent inhibition of PCa cells including C4-2B and 22Rv1 cell lines. The overexpression of the RORC gene activated the expression of ferroptosis-related proteins, such as FTH1, GPX4 and SLC7A11, and enhanced proliferation of PCa cells. WB experiments indicated that RORC upregulated AR and AR-V7. An enzalutamide-resistant C4-2B cell line revealed that RORC serves as a gene target for enzalutamide resistance. Finally, it was observed that ili-A could suppress CRPC cells proliferation by downregulating RORC expression, thereby promoting ferroptosis and enhancing the sensitivity to enzalutamide.
Conclusions: Ili-A inhibited RORC expression, increased malondialdehyde (MDA) content, suppressed glutathione (GSH) production, released free Fe2+, increased reactive oxygen species (ROS), activated the ferroptosis pathway, enhanced enzalutamide sensitivity, and inhibited CRPC cell proliferation. Furthermore, ili-A enhances the interaction between ROR-γ and GPX4.
背景：去势抵抗性前列腺癌（CRPC）患者在长期恩杂鲁胺治疗后经常出现耐药性。在前人研究的基础上，我们旨在进一步探讨ilicicolin A （ili-A）对恩杂鲁胺耐药的影响，并阐明其潜在的耐药机制。方法：采用5-乙基-2′-脱氧尿苷（EdU）法、菌落形成法、划痕法和Transwell法评价前列腺癌（PCa）细胞的增殖、迁移和侵袭。使用细胞计数试剂盒8 （CCK-8）评估药物对CRPC细胞的抑制效果。western blot （WB）检测肿瘤细胞凋亡蛋白和铁下垂的表达。采用共免疫沉淀法（Co-IP）和近端结扎法（PLA）研究了ilicicolin A与铁下垂的相互作用机制。用小鼠进行肿瘤移植实验来证实这一发现。结果：il - a对C4-2B和22Rv1细胞株均有剂量依赖性抑制作用。RORC基因的过表达激活了凋亡相关蛋白FTH1、GPX4、SLC7A11的表达，增强了PCa细胞的增殖。WB实验表明，RORC上调AR和AR- v7。对恩杂鲁胺耐药C4-2B细胞株的研究表明，RORC可作为恩杂鲁胺耐药的基因靶点。最后观察到il - a可通过下调RORC表达抑制CRPC细胞增殖，从而促进铁凋亡，增强对恩杂鲁胺的敏感性。结论：il - a抑制RORC表达，增加丙二醛（MDA）含量，抑制谷胱甘肽（GSH）产生，释放游离Fe2+，增加活性氧（ROS），激活铁凋亡途径，增强enzalutamide敏感性，抑制CRPC细胞增殖。此外，il - a增强了ROR-γ和GPX4之间的相互作用。
{"title":"Inhibition of the RORC/GPX4 mediated ferroptosis regulatory axis suppresses tumor growth and alleviates enzalutamide resistance in prostate cancer.","authors":"Yan Li, Bingqi Zhang, Zhongmin Zhang, Wei Yan, Haoyu Wang, Xun Xu, Anqi Lv, Zhengming Liao, Lang Guo","doi":"10.1186/s11658-025-00846-z","DOIUrl":"10.1186/s11658-025-00846-z","url":null,"abstract":"<p><strong>Background: </strong>Patients with castration-resistant prostate cancer (CRPC) often develop resistance following long-term enzalutamide treatment. Building upon previous research, we aims to further explore the effect of ilicicolin A (ili-A) on enzalutamide resistance and to elucidate the underlying resistance mechanisms.</p><p><strong>Methods: </strong>Proliferation, migration, and invasion of prostate cancer (PCa) cells were evaluated by 5-ethynyl-2'-deoxyuridine (EdU) assays, colony formation, scratch, and Transwell. Cell Counting Kit 8 (CCK-8) was used to assess the efficacy of drug inhibition in CRPC cells. The expression of tumor cell apoptotic proteins and ferroptosis was assessed using western blot (WB) analysis. Coimmunoprecipitation (Co-IP) and proximity ligation assay (PLA) were used to identify the mechanism of interaction between ilicicolin A and ferroptosis. Tumor transplantation experiments with mice were conducted to confirm findings.</p><p><strong>Results: </strong>Ili-A showed dose-dependent inhibition of PCa cells including C4-2B and 22Rv1 cell lines. The overexpression of the RORC gene activated the expression of ferroptosis-related proteins, such as FTH1, GPX4 and SLC7A11, and enhanced proliferation of PCa cells. WB experiments indicated that RORC upregulated AR and AR-V7. An enzalutamide-resistant C4-2B cell line revealed that RORC serves as a gene target for enzalutamide resistance. Finally, it was observed that ili-A could suppress CRPC cells proliferation by downregulating RORC expression, thereby promoting ferroptosis and enhancing the sensitivity to enzalutamide.</p><p><strong>Conclusions: </strong>Ili-A inhibited RORC expression, increased malondialdehyde (MDA) content, suppressed glutathione (GSH) production, released free Fe<sup>2+</sup>, increased reactive oxygen species (ROS), activated the ferroptosis pathway, enhanced enzalutamide sensitivity, and inhibited CRPC cell proliferation. Furthermore, ili-A enhances the interaction between ROR-γ and GPX4.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":" ","pages":"11"},"PeriodicalIF":10.2,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146043792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-24DOI: 10.1186/s11658-025-00841-4
Paulo Antas, Mariana D Machado, Fátima Leite-Pinheiro, Daniela Barros, Carlota Ramalhinho, Andreia Mendes, Beatriz H Ferreira, Daniela Carvoeiro, Luís F Mendes, Marisa Reverendo, Iola F Duarte, Miwako Narita, Bing Su, Rafael J Argüello, Beatrice Nal, Philippe Pierre, Catarina R Almeida, Evelina Gatti
Inhibition of the phosphatidylinositol kinase vacuolar protein sorting 34 (VPS34) with the pharmacological compound VPS34-IN1 has a range of effects on the dynamics of endosomes. While VPS34 inhibition has been previously suggested as a potential therapeutic approach for treating certain cancers, our findings indicate that it has minimal cytotoxic effects on the leukemic blastic plasmacytoid dendritic cell neoplasm (BPDCN) CAL-1. However, we also found that VPS34-IN1 interferes with the function of this plasmacytoid dendritic cell (pDC) line, by inhibiting Toll-like receptor (TLR)7 signaling. In contrast, VPS34-IN1 triggers activation of the stimulator of interferon genes (STING) and significantly enhances cellular response to the STING agonist 2'3'-cyclic guanosine monophosphate-adenosine monophosphate (2'3'-cGAMP) with increased expression of type I interferons (IFNs). Inhibition of protein synthesis by VPS34-IN1 appears to be central to this synergy with STING activation. Thus, despite their limited toxicity toward different cancer lines, VPS34-IN1 may represent a promising compound to promote expression of type I IFNs and thus antitumoral immunity.
{"title":"VPS34-IN1 potentiates STING-dependent activation in human CAL-1 cells.","authors":"Paulo Antas, Mariana D Machado, Fátima Leite-Pinheiro, Daniela Barros, Carlota Ramalhinho, Andreia Mendes, Beatriz H Ferreira, Daniela Carvoeiro, Luís F Mendes, Marisa Reverendo, Iola F Duarte, Miwako Narita, Bing Su, Rafael J Argüello, Beatrice Nal, Philippe Pierre, Catarina R Almeida, Evelina Gatti","doi":"10.1186/s11658-025-00841-4","DOIUrl":"10.1186/s11658-025-00841-4","url":null,"abstract":"<p><p>Inhibition of the phosphatidylinositol kinase vacuolar protein sorting 34 (VPS34) with the pharmacological compound VPS34-IN1 has a range of effects on the dynamics of endosomes. While VPS34 inhibition has been previously suggested as a potential therapeutic approach for treating certain cancers, our findings indicate that it has minimal cytotoxic effects on the leukemic blastic plasmacytoid dendritic cell neoplasm (BPDCN) CAL-1. However, we also found that VPS34-IN1 interferes with the function of this plasmacytoid dendritic cell (pDC) line, by inhibiting Toll-like receptor (TLR)7 signaling. In contrast, VPS34-IN1 triggers activation of the stimulator of interferon genes (STING) and significantly enhances cellular response to the STING agonist 2'3'-cyclic guanosine monophosphate-adenosine monophosphate (2'3'-cGAMP) with increased expression of type I interferons (IFNs). Inhibition of protein synthesis by VPS34-IN1 appears to be central to this synergy with STING activation. Thus, despite their limited toxicity toward different cancer lines, VPS34-IN1 may represent a promising compound to promote expression of type I IFNs and thus antitumoral immunity.</p>","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":" ","pages":"24"},"PeriodicalIF":10.2,"publicationDate":"2026-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12910983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146043757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-22DOI: 10.1186/s11658-025-00856-x
Junren Chen, Siqi Qin, Ziwei Xing, Feng Wan, Jie Yin, Cheng Peng, Dan Li
{"title":"Targeting the sirtuin 6-NF-κB p65 axis by 6-hydroxyhyoscyamine hydrobromide: a deacetylation-driven new therapy for diabetic wounds.","authors":"Junren Chen, Siqi Qin, Ziwei Xing, Feng Wan, Jie Yin, Cheng Peng, Dan Li","doi":"10.1186/s11658-025-00856-x","DOIUrl":"10.1186/s11658-025-00856-x","url":null,"abstract":"","PeriodicalId":9688,"journal":{"name":"Cellular & Molecular Biology Letters","volume":" ","pages":"23"},"PeriodicalIF":10.2,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12910970/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146028529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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