Pyrolyzed deketene curcumin controls regulatory T cell generation and gastric cancer metabolism cooperate with 2-deoxy-d-glucose
Pyrolyzed deketene curcumin GO-Y022 prevents carcinogenesis in a gastric cancer mouse model. However, it is still less clear if GO-Y022 affects tumor-induced immune suppression. In this study, we found that GO-Y022 inhibited Treg generation in the presence of transforming growth factor beta 1 (TGF-β...
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| Format: | Article |
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Frontiers Media S.A.
2023-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1049713/full |
| _version_ | 1811170976253083648 |
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| author | Takashi MaruYama Takashi MaruYama Takashi MaruYama Hirofumi Miyazaki Yun-Ji Lim Jian Gu Jian Gu Masaki Ishikawa Taichi Yoshida WanJun Chen Yuji Owada Hiroyuki Shibata |
| author_facet | Takashi MaruYama Takashi MaruYama Takashi MaruYama Hirofumi Miyazaki Yun-Ji Lim Jian Gu Jian Gu Masaki Ishikawa Taichi Yoshida WanJun Chen Yuji Owada Hiroyuki Shibata |
| author_sort | Takashi MaruYama |
| collection | DOAJ |
| description | Pyrolyzed deketene curcumin GO-Y022 prevents carcinogenesis in a gastric cancer mouse model. However, it is still less clear if GO-Y022 affects tumor-induced immune suppression. In this study, we found that GO-Y022 inhibited Treg generation in the presence of transforming growth factor beta 1 (TGF-β). However, GO-Y022 showed less impact on Foxp3+ Tregs in the gastric tumor microenvironment. Gastric tumor cells produce a large amount of L-lactate in the presence of GO-Y022 and diminish the inhibitory role of GO-Y022 against Treg generation in response to TGF-β. Therefore, naïve CD4+ T cells co-cultured with GO-Y022 treated gastric tumor cells increased Treg generation. GO-Y022-induced tumor cell death was further enhanced by 2-deoxy-d-glucose (2DG), a glycolysis inhibitor. Combination treatment of GO-Y022 and 2DG results in reduced L-lactate production and Treg generation in gastric tumor cells. Overall, GO-Y022-treatment with restricted glucose metabolism inhibits gastric tumor cell survival and promotes anti-tumor immunity. |
| first_indexed | 2024-04-10T17:05:45Z |
| format | Article |
| id | doaj.art-f7013cfc9de84921832b3b6046d45e8f |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-10T17:05:45Z |
| publishDate | 2023-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-f7013cfc9de84921832b3b6046d45e8f2023-02-06T05:30:08ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-02-011410.3389/fimmu.2023.10497131049713Pyrolyzed deketene curcumin controls regulatory T cell generation and gastric cancer metabolism cooperate with 2-deoxy-d-glucoseTakashi MaruYama0Takashi MaruYama1Takashi MaruYama2Hirofumi Miyazaki3Yun-Ji Lim4Jian Gu5Jian Gu6Masaki Ishikawa7Taichi Yoshida8WanJun Chen9Yuji Owada10Hiroyuki Shibata11Mucosal Immunology Section, National Institute of Dental and Craniofacial Research (NIDCR), National Institute of Health, Bethesda, MD, United StatesDepartment of Immunology, Graduate School of Medicine, Akita University, Akita, JapanDepartment of Organ Anatomy, Graduate School of Medicine, Tohoku University, Sendai, JapanDepartment of Organ Anatomy, Graduate School of Medicine, Tohoku University, Sendai, JapanMucosal Immunology Section, National Institute of Dental and Craniofacial Research (NIDCR), National Institute of Health, Bethesda, MD, United StatesHepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University and Research Unit of Liver Transplantation and Transplant Immunology, Chinese Academy of Medical Sciences, Nanjing, ChinaJiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, ChinaThe Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United StatesDepartment of Clinical Oncology, Graduate School of Medicine, Akita University, Akita, JapanMucosal Immunology Section, National Institute of Dental and Craniofacial Research (NIDCR), National Institute of Health, Bethesda, MD, United StatesDepartment of Organ Anatomy, Graduate School of Medicine, Tohoku University, Sendai, JapanDepartment of Clinical Oncology, Graduate School of Medicine, Akita University, Akita, JapanPyrolyzed deketene curcumin GO-Y022 prevents carcinogenesis in a gastric cancer mouse model. However, it is still less clear if GO-Y022 affects tumor-induced immune suppression. In this study, we found that GO-Y022 inhibited Treg generation in the presence of transforming growth factor beta 1 (TGF-β). However, GO-Y022 showed less impact on Foxp3+ Tregs in the gastric tumor microenvironment. Gastric tumor cells produce a large amount of L-lactate in the presence of GO-Y022 and diminish the inhibitory role of GO-Y022 against Treg generation in response to TGF-β. Therefore, naïve CD4+ T cells co-cultured with GO-Y022 treated gastric tumor cells increased Treg generation. GO-Y022-induced tumor cell death was further enhanced by 2-deoxy-d-glucose (2DG), a glycolysis inhibitor. Combination treatment of GO-Y022 and 2DG results in reduced L-lactate production and Treg generation in gastric tumor cells. Overall, GO-Y022-treatment with restricted glucose metabolism inhibits gastric tumor cell survival and promotes anti-tumor immunity.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1049713/fulltumor microenvironmentstomach neoplasmsadenosine triphosphateglycolysisregulatory T cells |
| spellingShingle | Takashi MaruYama Takashi MaruYama Takashi MaruYama Hirofumi Miyazaki Yun-Ji Lim Jian Gu Jian Gu Masaki Ishikawa Taichi Yoshida WanJun Chen Yuji Owada Hiroyuki Shibata Pyrolyzed deketene curcumin controls regulatory T cell generation and gastric cancer metabolism cooperate with 2-deoxy-d-glucose Frontiers in Immunology tumor microenvironment stomach neoplasms adenosine triphosphate glycolysis regulatory T cells |
| title | Pyrolyzed deketene curcumin controls regulatory T cell generation and gastric cancer metabolism cooperate with 2-deoxy-d-glucose |
| title_full | Pyrolyzed deketene curcumin controls regulatory T cell generation and gastric cancer metabolism cooperate with 2-deoxy-d-glucose |
| title_fullStr | Pyrolyzed deketene curcumin controls regulatory T cell generation and gastric cancer metabolism cooperate with 2-deoxy-d-glucose |
| title_full_unstemmed | Pyrolyzed deketene curcumin controls regulatory T cell generation and gastric cancer metabolism cooperate with 2-deoxy-d-glucose |
| title_short | Pyrolyzed deketene curcumin controls regulatory T cell generation and gastric cancer metabolism cooperate with 2-deoxy-d-glucose |
| title_sort | pyrolyzed deketene curcumin controls regulatory t cell generation and gastric cancer metabolism cooperate with 2 deoxy d glucose |
| topic | tumor microenvironment stomach neoplasms adenosine triphosphate glycolysis regulatory T cells |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1049713/full |
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