Epigallocatechin‑3‑gallate hinders metabolic coupling to suppress colorectal cancer malignancy through targeting aerobic glycolysis in cancer‑associated fibroblasts

Chen,Shuhai; Nishi,Masaaki; Morine,Yuji; Shimada,Mitsuo; Tokunaga,Takuya; Kashihara,Hideya; Takasu,Chie; Yamada,Shinichiro; Wada,Yuma

doi:10.3892/ijo.2022.5309

Epigallocatechin‑3‑gallate hinders metabolic coupling to suppress colorectal cancer malignancy through targeting aerobic glycolysis in cancer‑associated fibroblasts

Authors:
- Shuhai Chen
- Masaaki Nishi
- Yuji Morine
- Mitsuo Shimada
- Takuya Tokunaga
- Hideya Kashihara
- Chie Takasu
- Shinichiro Yamada
- Yuma Wada
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Affiliations: Department of Surgery, Institute of Biomedical Sciences, Tokushima University, Tokushima 770‑8503, Japan
Published online on: January 14, 2022 https://doi.org/10.3892/ijo.2022.5309
Article Number: 19
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

In recent times, researchers working on tumor metabolism have paid increasing attention to the tumor microenvironment. Emerging evidence has confirmed that epigenetic modifications of cancer‑associated fibroblasts (CAFs) alters the characteristics of glucose metabolism to achieve a symbiotic relationship with the cancer cells. Epigallocatechin‑3‑gallate (EGCG) exerts anti‑tumor effects via a variety of mechanisms, although the underlying mechanism that accounts for the effects of EGCG on glucose metabolic alterations of CAFs have yet to be elucidated. In the present study, through co‑culture with colorectal cancer (CRC) cells, human intestinal fibroblasts were transformed into CAFs, and exhibited enhanced aerobic glycolysis. Induced CAFs were able to enhance the proliferation, migration and invasion of CRC cells in vitro. EGCG treatment led to direct inhibition of the proliferation and migration of CRC cells; furthermore, EGCG treatment of CAFs suppressed their tumor‑promoting capabilities by inhibiting their glycolytic activity. Blocking the lactic acid efflux of CAFs with a monocarboxylate transporter 4 (MCT4) inhibitor or through silencing MCT4 could also suppress their tumor‑promoting capabilities, indicating that lactate fulfills an important role in the metabolic coupling that occurs between CAFs and cancer cells. Taken together, the results of the present study showed that EGCG targeting of the metabolism of tumor stromal cells provided a safe and effective strategy of anti‑cancer therapy.

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