Pyrolyzed deketene curcumin controls regulatory T cell generation and gastric cancer metabolism cooperate with 2-deoxy-d-glucose

Takashi Maruyama; Hirofumi Miyazaki; Yun Ji Lim; Jian Gu; Masaki Ishikawa; Taichi Yoshida; Wan Jun Chen; Yuji Owada; Hiroyuki Shibata

doi:10.3389/fimmu.2023.1049713

Pyrolyzed deketene curcumin controls regulatory T cell generation and gastric cancer metabolism cooperate with 2-deoxy-d-glucose

Takashi Maruyama, Hirofumi Miyazaki, Yun Ji Lim, Jian Gu, Masaki Ishikawa, Taichi Yoshida, Wan Jun Chen, Yuji Owada, Hiroyuki Shibata

MED - Medical Sciences

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Article number	1049713
Journal	Frontiers in immunology
Volume	14
DOIs	https://doi.org/10.3389/fimmu.2023.1049713
Publication status	Published - 2023 Feb 6

Keywords

adenosine triphosphate
glycolysis
regulatory T cells
stomach neoplasms
tumor microenvironment

ASJC Scopus subject areas

Immunology and Allergy
Immunology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.3389/fimmu.2023.1049713

Cite this

@article{a0dcbb545d5b45d7828a795a8589da42,

title = "Pyrolyzed deketene curcumin controls regulatory T cell generation and gastric cancer metabolism cooperate with 2-deoxy-d-glucose",

abstract = "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, na{\"i}ve 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.",

keywords = "adenosine triphosphate, glycolysis, regulatory T cells, stomach neoplasms, tumor microenvironment",

author = "Takashi Maruyama and Hirofumi Miyazaki and Lim, {Yun Ji} and Jian Gu and Masaki Ishikawa and Taichi Yoshida and Chen, {Wan Jun} and Yuji Owada and Hiroyuki Shibata",

note = "Funding Information: This research was supported in part by the Intramural Research Program of NIDCR, NIH to WC, and a Grant-in-Aid for Scientific Research (C) (20K11643) to HS. Acknowledgments Funding Information: This study was supported in part by the Combined Technical Research Core at the NIDCR, NIH. We are grateful to Maya Chiba (Akita University, Department of Clinical Oncology) and Shuhei Kobayashi (Tohoku University, Department of Organ Anatomy) for their technical assistance. We are also grateful to Tatsushi Muta (Tohoku University) () for providing critical materials. Publisher Copyright: Copyright {\textcopyright} 2023 MaruYama, Miyazaki, Lim, Gu, Ishikawa, Yoshida, Chen, Owada and Shibata.",

year = "2023",

month = feb,

day = "6",

doi = "10.3389/fimmu.2023.1049713",

language = "English",

volume = "14",

journal = "Frontiers in Immunology",

issn = "1664-3224",

publisher = "Frontiers Media S. A.",

}

TY - JOUR

T1 - Pyrolyzed deketene curcumin controls regulatory T cell generation and gastric cancer metabolism cooperate with 2-deoxy-d-glucose

AU - Maruyama, Takashi

AU - Miyazaki, Hirofumi

AU - Lim, Yun Ji

AU - Gu, Jian

AU - Ishikawa, Masaki

AU - Yoshida, Taichi

AU - Chen, Wan Jun

AU - Owada, Yuji

AU - Shibata, Hiroyuki

N1 - Funding Information: This research was supported in part by the Intramural Research Program of NIDCR, NIH to WC, and a Grant-in-Aid for Scientific Research (C) (20K11643) to HS. Acknowledgments Funding Information: This study was supported in part by the Combined Technical Research Core at the NIDCR, NIH. We are grateful to Maya Chiba (Akita University, Department of Clinical Oncology) and Shuhei Kobayashi (Tohoku University, Department of Organ Anatomy) for their technical assistance. We are also grateful to Tatsushi Muta (Tohoku University) () for providing critical materials. Publisher Copyright: Copyright © 2023 MaruYama, Miyazaki, Lim, Gu, Ishikawa, Yoshida, Chen, Owada and Shibata.

PY - 2023/2/6

Y1 - 2023/2/6

N2 - 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.

AB - 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.

KW - adenosine triphosphate

KW - glycolysis

KW - regulatory T cells

KW - stomach neoplasms

KW - tumor microenvironment

UR - http://www.scopus.com/inward/record.url?scp=85148524818&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85148524818&partnerID=8YFLogxK

U2 - 10.3389/fimmu.2023.1049713

DO - 10.3389/fimmu.2023.1049713

M3 - Article

C2 - 36814928

AN - SCOPUS:85148524818

SN - 1664-3224

VL - 14

JO - Frontiers in Immunology

JF - Frontiers in Immunology

M1 - 1049713

ER -

Pyrolyzed deketene curcumin controls regulatory T cell generation and gastric cancer metabolism cooperate with 2-deoxy-d-glucose

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this