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Using Mouse Mammary Tumor Cells to Teach Core Biology Concepts: A Simple Lab Module
Published on: June 18, 2015
Pyrolyzed deketene curcumin controls regulatory T cell generation and gastric cancer metabolism cooperate with
Takashi MaruYama1,2,3, Hirofumi Miyazaki3, Yun-Ji Lim1
1Mucosal Immunology Section, National Institute of Dental and Craniofacial Research (NIDCR), National Institute of Health, Bethesda, MD, United States.
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.
Insights
Pyrolyzed deketene curcumin GO-Y022 inhibits gastric tumor growth by restricting glucose metabolism and promoting anti-tumor immunity. This compound reduces L-lactate production and Treg generation in gastric cancer cells.
Area of Science:
- Immunology
- Oncology
- Biochemistry
Background:
- Pyrolyzed deketene curcumin GO-Y022 demonstrates anti-carcinogenic effects in gastric cancer models.
- The impact of GO-Y022 on tumor-induced immune suppression, particularly regulatory T cells (Tregs), remains unclear.
Purpose of the Study:
- To investigate the effect of GO-Y022 on Treg generation in gastric cancer.
- To elucidate the mechanisms by which gastric tumor cells modulate GO-Y022's anti-Treg activity.
Main Methods:
- Investigated GO-Y022's effect on Treg generation in vitro with transforming growth factor beta 1 (TGF-β).
- Analyzed L-lactate production by gastric tumor cells treated with GO-Y022.
- Co-cultured naïve CD4+ T cells with GO-Y022 treated gastric tumor cells.
- Assessed the impact of 2-deoxy-d-glucose (2DG), a glycolysis inhibitor, in combination with GO-Y022.
Main Results:
- GO-Y022 inhibited Treg generation induced by TGF-β but had limited effect on established Foxp3+ Tregs in the tumor microenvironment.
- Gastric tumor cells treated with GO-Y022 increased L-lactate production, counteracting GO-Y022's inhibitory effect on Treg generation.
- Co-culture with GO-Y022 treated tumor cells enhanced Treg generation.
- Combination treatment with GO-Y022 and 2DG reduced L-lactate production and Treg generation.
- Combined therapy enhanced GO-Y022-induced tumor cell death.
Conclusions:
- GO-Y022, when combined with restricted glucose metabolism (e.g., using 2DG), effectively inhibits gastric tumor cell survival.
- This combined approach promotes anti-tumor immunity by reducing Treg generation and L-lactate production.

