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Article: Glutamic-Pyruvic Transaminase 1 Facilitates Alternative Fuels for Hepatocellular Carcinoma Growth—A Small Molecule Inhibitor, Berberine
Title | Glutamic-Pyruvic Transaminase 1 Facilitates Alternative Fuels for Hepatocellular Carcinoma Growth—A Small Molecule Inhibitor, Berberine |
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Authors | |
Keywords | metabolic reprogramming hepatocellular carcinoma glucose–alanine cycle GPT1 berberine |
Issue Date | 2020 |
Publisher | MDPI AG. The Journal's web site is located at http://www.mdpi.com/journal/cancers/ |
Citation | Cancers, 2020, v. 12 n. 7, p. article no. 1854 How to Cite? |
Abstract | Metabolic reprogramming is an essential hallmark of cancer. Besides the “Warburg effect”, cancer cells also actively reprogram amino acid metabolism to satisfy high nutritional demands in a nutrient-poor environment. In the glucose–alanine cycle, exogenous alanine taken up by hepatocytes is converted to pyruvate via glutamic-pyruvic transaminases (GPTs). However, the precise role of the glucose–alanine cycle in hepatocellular carcinoma (HCC) remains elusive. The current study revealed that alanine, as an alternative energy source, induced the metabolic reprogramming of HCC cells via activation of the downstream glucose–alanine cycle and thus promoted HCC growth in nutrient-depleted conditions. Further overexpression and loss-of-function studies indicated that GPT1 was an essential regulator for alanine-supplemented HCC growth. Combining molecular docking and metabolomics analyses, our study further identified a naturally occurring alkaloid, berberine (BBR), as the GPT1 inhibitor in HCC. Mechanically, BBR-mediated metabolic reprogramming of alanine-supplemented HCC via GPT1 suppression attenuated adenosine triphosphate (ATP) production and thus suppressed HCC growth. In conclusion, our study suggests that GPT1-mediated alanine–glucose conversion may be a potential molecular target for HCC therapy. Further demonstration of BBR-mediated metabolic reprogramming of HCC would contribute to the development of this Chinese medicine-derived compound as an adjuvant therapy for HCC. |
Persistent Identifier | http://hdl.handle.net/10722/284275 |
ISSN | 2023 Impact Factor: 4.5 2023 SCImago Journal Rankings: 1.391 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | GUO, W | - |
dc.contributor.author | Tan, HY | - |
dc.contributor.author | Li, S | - |
dc.contributor.author | Wang, N | - |
dc.contributor.author | Feng, Y | - |
dc.date.accessioned | 2020-07-20T05:57:26Z | - |
dc.date.available | 2020-07-20T05:57:26Z | - |
dc.date.issued | 2020 | - |
dc.identifier.citation | Cancers, 2020, v. 12 n. 7, p. article no. 1854 | - |
dc.identifier.issn | 2072-6694 | - |
dc.identifier.uri | http://hdl.handle.net/10722/284275 | - |
dc.description.abstract | Metabolic reprogramming is an essential hallmark of cancer. Besides the “Warburg effect”, cancer cells also actively reprogram amino acid metabolism to satisfy high nutritional demands in a nutrient-poor environment. In the glucose–alanine cycle, exogenous alanine taken up by hepatocytes is converted to pyruvate via glutamic-pyruvic transaminases (GPTs). However, the precise role of the glucose–alanine cycle in hepatocellular carcinoma (HCC) remains elusive. The current study revealed that alanine, as an alternative energy source, induced the metabolic reprogramming of HCC cells via activation of the downstream glucose–alanine cycle and thus promoted HCC growth in nutrient-depleted conditions. Further overexpression and loss-of-function studies indicated that GPT1 was an essential regulator for alanine-supplemented HCC growth. Combining molecular docking and metabolomics analyses, our study further identified a naturally occurring alkaloid, berberine (BBR), as the GPT1 inhibitor in HCC. Mechanically, BBR-mediated metabolic reprogramming of alanine-supplemented HCC via GPT1 suppression attenuated adenosine triphosphate (ATP) production and thus suppressed HCC growth. In conclusion, our study suggests that GPT1-mediated alanine–glucose conversion may be a potential molecular target for HCC therapy. Further demonstration of BBR-mediated metabolic reprogramming of HCC would contribute to the development of this Chinese medicine-derived compound as an adjuvant therapy for HCC. | - |
dc.language | eng | - |
dc.publisher | MDPI AG. The Journal's web site is located at http://www.mdpi.com/journal/cancers/ | - |
dc.relation.ispartof | Cancers | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.subject | metabolic reprogramming | - |
dc.subject | hepatocellular carcinoma | - |
dc.subject | glucose–alanine cycle | - |
dc.subject | GPT1 | - |
dc.subject | berberine | - |
dc.title | Glutamic-Pyruvic Transaminase 1 Facilitates Alternative Fuels for Hepatocellular Carcinoma Growth—A Small Molecule Inhibitor, Berberine | - |
dc.type | Article | - |
dc.identifier.email | Tan, HY: hyhtan@hku.hk | - |
dc.identifier.email | Li, S: lishaha@hku.hk | - |
dc.identifier.email | Wang, N: ckwang@hku.hk | - |
dc.identifier.email | Feng, Y: yfeng@hku.hk | - |
dc.identifier.authority | Wang, N=rp02075 | - |
dc.identifier.authority | Feng, Y=rp00466 | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.3390/cancers12071854 | - |
dc.identifier.scopus | eid_2-s2.0-85087763237 | - |
dc.identifier.hkuros | 311478 | - |
dc.identifier.volume | 12 | - |
dc.identifier.issue | 7 | - |
dc.identifier.spage | article no. 1854 | - |
dc.identifier.epage | article no. 1854 | - |
dc.identifier.isi | WOS:000557939500001 | - |
dc.publisher.place | Switzerland | - |
dc.identifier.issnl | 2072-6694 | - |