Impact of Exogenous Treatment with Histidine on Hepatocellular Carcinoma Cells
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 v...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-02-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/5/1205 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Yusun Park |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T20:46:15Z |
| format | Article |
| id | doaj.art-ffc453d1bfac43e7b2c3a604d5799f88 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T20:46:15Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-ffc453d1bfac43e7b2c3a604d5799f882023-11-23T22:47:27ZengMDPI AGCancers2072-66942022-02-01145120510.3390/cancers14051205Impact of Exogenous Treatment with Histidine on Hepatocellular Carcinoma CellsYusun Park0Yeonju Han1Dongwoo Kim2Sua Cho3WonJin Kim4Hyemin Hwang5Hye Won Lee6Dai Hoon Han7Kyung Sik Kim8Mijin Yun9Misu Lee10Division of Life Sciences, College of Life Science and Bioengineering, Incheon National University, Incheon 22012, KoreaDivision of Life Sciences, College of Life Science and Bioengineering, Incheon National University, Incheon 22012, KoreaDepartment of Nuclear Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, KoreaDivision of Life Sciences, College of Life Science and Bioengineering, Incheon National University, Incheon 22012, KoreaDivision of Life Sciences, College of Life Science and Bioengineering, Incheon National University, Incheon 22012, KoreaDivision of Life Sciences, College of Life Science and Bioengineering, Incheon National University, Incheon 22012, KoreaDepartment of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, KoreaDepartment of Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, KoreaDepartment of Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, KoreaDepartment of Nuclear Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, KoreaDivision of Life Sciences, College of Life Science and Bioengineering, Incheon National University, Incheon 22012, KoreaHepatocellular 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.https://www.mdpi.com/2072-6694/14/5/1205hepatocellular carcinomasorafenibcancer metabolismhistidinedrug sensitivity |
| spellingShingle | 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 Impact of Exogenous Treatment with Histidine on Hepatocellular Carcinoma Cells Cancers hepatocellular carcinoma sorafenib cancer metabolism histidine drug sensitivity |
| title | Impact of Exogenous Treatment with Histidine on Hepatocellular Carcinoma Cells |
| title_full | Impact of Exogenous Treatment with Histidine on Hepatocellular Carcinoma Cells |
| title_fullStr | Impact of Exogenous Treatment with Histidine on Hepatocellular Carcinoma Cells |
| title_full_unstemmed | Impact of Exogenous Treatment with Histidine on Hepatocellular Carcinoma Cells |
| title_short | Impact of Exogenous Treatment with Histidine on Hepatocellular Carcinoma Cells |
| title_sort | impact of exogenous treatment with histidine on hepatocellular carcinoma cells |
| topic | hepatocellular carcinoma sorafenib cancer metabolism histidine drug sensitivity |
| url | https://www.mdpi.com/2072-6694/14/5/1205 |
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