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Impact of Exogenous Treatment with Histidine on Hepatocellular Carcinoma Cells

 Yusun Park  ;  Yeonju Han  ;  Dongwoo Kim  ;  Sua Cho  ;  WonJin Kim  ;  Hyemin Hwang  ;  Hye Won Lee  ;  Dai Hoon Han  ;  Kyung Sik Kim  ;  Mijin Yun  ;  Misu Lee 
 CANCERS, Vol.14(5) : 1205, 2022-02 
Journal Title
Issue Date
cancer metabolism ; drug sensitivity ; hepatocellular carcinoma ; histidine ; sorafenib
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Sorafenib, a multi-kinase inhibitor, is the first-line therapy for advanced HCC. However, long-term exposure to sorafenib often results in reduced sensitivity and the development of resistance. Although various amino acids have been shown to contribute to cancer initiation and progression, little is known about the effects of histidine, a dietary essential amino acid that is partially taken up via histidine/large neutral amino acid transporter (LAT1), on cancer cells. In this study, we evaluated the effects of histidine on HCC cells and sensitivity to sorafenib. Remarkably, we found that exogenous histidine treatment induced a reduction in the expression of tumor markers related to glycolysis (GLUT1 and HK2), inflammation (STAT3), angiogenesis (VEGFB and VEGFC), and stem cells (CD133). In addition, LAT1 expression was downregulated in HCC tumor regions with high expression of GLUT1, CD133, and pSTAT3, which are known to induce sorafenib resistance. Finally, we demonstrated that combined treatment with sorafenib and histidine could be a novel therapeutic strategy to enhance the sensitivity to sorafenib, thereby improving long-term survival in HCC.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Nuclear Medicine (핵의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kyung Sik(김경식) ORCID logo https://orcid.org/0000-0001-9498-284X
Kim, Dongwoo(김동우) ORCID logo https://orcid.org/0000-0002-1723-604X
Yun, Mi Jin(윤미진) ORCID logo https://orcid.org/0000-0002-1712-163X
Lee, Hye Won(이혜원) ORCID logo https://orcid.org/0000-0002-3552-3560
Han, Dai Hoon(한대훈) ORCID logo https://orcid.org/0000-0003-2787-7876
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