Aerobic glycolysis in colon cancer is repressed by naringin via the <i>HIF1Α</i> pathway.

Guangtao Pan; Ping Zhang; Aiying Chen; Yu Deng; Zhen Zhang; Han LU; Aoxun Zhu; Cong Zhou; Yanran WU; Sen LI

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Aerobic glycolysis in colon cancer is repressed by naringin via the HIF1Α pathway.

Author: Guangtao PAN ¹ ; Ping ZHANG ² ; Aiying CHEN ³ ; Yu DENG ² ; Zhen ZHANG ¹ ; Han LU ¹ ; Aoxun ZHU ¹ ; Cong ZHOU ² ; Yanran WU ⁴ ; Sen LI ⁵
Author Information

1. Yancheng TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Yancheng 224000, China.
2. Hubei University of Chinese Medicine, Wuhan 430000, China.
3. Nanjing University of Chinese Medicine, Nanjing 210033, China.
4. Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China. wuyanran196512@163.com.
5. Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China. lisentome728@hotmail.com.
Publication Type:Journal Article
Keywords: Colon cancer; Enolase 2 (ENO2); Glycolysis; Hypoxia inducible factor-1α (HIF1Α); Metabolic reprogramming; Naringin
MeSH: Glycolysis; Colonic Neoplasms/metabolism*; Humans; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism*; Phosphopyruvate Hydratase/metabolism*; Flavanones/pharmacology*; Cell Line, Tumor; Databases, Genetic; Cell Proliferation/drug effects*; Transfection; Warburg Effect, Oncologic
From: Journal of Zhejiang University. Science. B 2023;24(3):221-231
CountryChina
Language:English
Abstract: Metabolic reprogramming is a common phenomenon in cancer, with aerobic glycolysis being one of its important characteristics. Hypoxia-inducible factor-1α (HIF1Α) is thought to play an important role in aerobic glycolysis. Meanwhile, naringin is a natural flavanone glycoside derived from grapefruits and many other citrus fruits. In this work, we identified glycolytic genes related to HIF1Α by analyzing the colon cancer database. The analysis of extracellular acidification rate and cell function verified the regulatory effects of HIF1Α overexpression on glycolysis, and the proliferation and migration of colon cancer cells. Moreover, naringin was used as an inhibitor of colon cancer cells to illustrate its effect on HIF1Α function. The results showed that the HIF1Α and enolase 2 (ENO2) levels in colon cancer tissues were highly correlated, and their high expression indicated a poor prognosis for colon cancer patients. Mechanistically, HIF1Α directly binds to the DNA promoter region and upregulates the transcription of ENO2; ectopic expression of ENO2 increased aerobic glycolysis in colon cancer cells. Most importantly, we found that the appropriate concentration of naringin inhibited the transcriptional activity of HIF1Α, which in turn decreased aerobic glycolysis in colon cancer cells. Generally, naringin reduces glycolysis in colon cancer cells by reducing the transcriptional activity of HIF1Α and the proliferation and invasion of colon cancer cells. This study helps to elucidate the relationship between colon cancer progression and glucose metabolism, and demonstrates the efficacy of naringin in the treatment of colon cancer.