Berberine decelerates glucose metabolism via suppression of mTOR‑dependent HIF‑1α protein synthesis in colon cancer cells

Mao,Liyuan; Chen,Qiongyun; Gong,Ke; Xu,Xiaolin; Xie,Yurou; Zhang,Wenqing; Cao,Hanwei; Hu,Tianhui; Hong,Xiaoting; Zhan,Yan‑Yan

doi:10.3892/or.2018.6318

Berberine decelerates glucose metabolism via suppression of mTOR‑dependent HIF‑1α protein synthesis in colon cancer cells

Authors:
- Liyuan Mao
- Qiongyun Chen
- Ke Gong
- Xiaolin Xu
- Yurou Xie
- Wenqing Zhang
- Hanwei Cao
- Tianhui Hu
- Xiaoting Hong
- Yan‑Yan Zhan
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Affiliations: Cancer Research Center, Medical College of Xiamen University, Xiamen, Fujian 361102, P.R. China
Published online on: March 16, 2018 https://doi.org/10.3892/or.2018.6318
Pages: 2436-2442

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Abstract

Hyperactivated glucose uptake and glycolytic metabolism are considered as a hallmark of cancer. Berberine, a natural alkaloid with tumor‑selective anticancer effects, has been shown to promote glucose uptake in metabolic tissues and cells. However, whether and how berberine regulates the glucose metabolism of cancer cells are still poorly understood. In the present study, we revealed that berberine, which suppressed the growth of colon cancer cell lines HCT116 and KM12C, greatly inhibited the glucose uptake and the transcription of glucose metabolic genes, GLUT1, LDHA and HK2 in these two cell lines as assessed by RT‑qPCR. A mechanistic study further indicated that the protein expression but not mRNA transcription of HIF‑1α, a well‑known transcription factor critical for dysregulated cancer cell glucose metabolism, was dramatically inhibited in berberine‑treated colon cancer cell lines. Using western blot analysis, this regulation appears to occur via protein synthesis but not protein stability as blockade of HIF‑1α protein degradation by hypoxia mimic desferrioxamine (DFX) or proteasome inhibitor MG132 did not affect berberine's effect. In addition, mTOR signaling previously reported to regulate HIF‑1α protein synthesis was further found to be suppressed by berberine. Taken together, our results indicated that berberine inhibits overactive glucose metabolism of colon cancer cells via suppressing mTOR‑depended HIF‑1α protein synthesis, which provided not only a novel mechanism involved in berberine's tumor‑specific toxicity but also a theoretical basis for the development of berberine for colon cancer treatment.

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