Berberine decelerates glucose metabolism via suppression of mTOR‑dependent HIF‑1α protein synthesis in colon cancer cells
Autor: | Xiaoting Hong, Xiaolin Xu, Ke Gong, Wenqing Zhang, Liyuan Mao, Yan‑Yan Zhan, Yurou Xie, Tianhui Hu, Qiongyun Chen, Hanwei Cao |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Cancer Research Berberine Glucose uptake Down-Regulation Protein degradation 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell Line Tumor Hexokinase Humans PI3K/AKT/mTOR pathway Cell Proliferation Glucose Transporter Type 1 biology L-Lactate Dehydrogenase Chemistry Cell growth TOR Serine-Threonine Kinases General Medicine HCT116 Cells Hypoxia-Inducible Factor 1 alpha Subunit Gene Expression Regulation Neoplastic Isoenzymes 030104 developmental biology Glucose Oncology 030220 oncology & carcinogenesis Cancer cell Colonic Neoplasms biology.protein Cancer research GLUT1 Lactate Dehydrogenase 5 Signal Transduction |
Zdroj: | Oncology reports. 39(5) |
ISSN: | 1791-2431 |
Popis: | 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. |
Databáze: | OpenAIRE |
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