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Article: Glutamic-Pyruvic Transaminase 1 Facilitates Alternative Fuels for Hepatocellular Carcinoma Growth—A Small Molecule Inhibitor, Berberine

TitleGlutamic-Pyruvic Transaminase 1 Facilitates Alternative Fuels for Hepatocellular Carcinoma Growth—A Small Molecule Inhibitor, Berberine
Authors
Keywordsmetabolic reprogramming
hepatocellular carcinoma
glucose–alanine cycle
GPT1
berberine
Issue Date2020
PublisherMDPI 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?
AbstractMetabolic 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 Identifierhttp://hdl.handle.net/10722/284275
ISSN
2018 Impact Factor: 6.162
2015 SCImago Journal Rankings: 1.630

 

DC FieldValueLanguage
dc.contributor.authorGUO, W-
dc.contributor.authorTan, HY-
dc.contributor.authorLi, S-
dc.contributor.authorWang, N-
dc.contributor.authorFeng, Y-
dc.date.accessioned2020-07-20T05:57:26Z-
dc.date.available2020-07-20T05:57:26Z-
dc.date.issued2020-
dc.identifier.citationCancers, 2020, v. 12 n. 7, p. article no. 1854-
dc.identifier.issn2072-6694-
dc.identifier.urihttp://hdl.handle.net/10722/284275-
dc.description.abstractMetabolic 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.languageeng-
dc.publisherMDPI AG. The Journal's web site is located at http://www.mdpi.com/journal/cancers/-
dc.relation.ispartofCancers-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectmetabolic reprogramming-
dc.subjecthepatocellular carcinoma-
dc.subjectglucose–alanine cycle-
dc.subjectGPT1-
dc.subjectberberine-
dc.titleGlutamic-Pyruvic Transaminase 1 Facilitates Alternative Fuels for Hepatocellular Carcinoma Growth—A Small Molecule Inhibitor, Berberine-
dc.typeArticle-
dc.identifier.emailTan, HY: hyhtan@hku.hk-
dc.identifier.emailLi, S: lishaha@hku.hk-
dc.identifier.emailWang, N: ckwang@hku.hk-
dc.identifier.emailFeng, Y: yfeng@hku.hk-
dc.identifier.authorityWang, N=rp02075-
dc.identifier.authorityFeng, Y=rp00466-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.3390/cancers12071854-
dc.identifier.scopuseid_2-s2.0-85087763237-
dc.identifier.hkuros311478-
dc.identifier.volume12-
dc.identifier.issue7-
dc.identifier.spagearticle no. 1854-
dc.identifier.epagearticle no. 1854-
dc.publisher.placeSwitzerland-

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