IDO Inhibitor and Gallic Acid Cross-Linked Small Molecule Drug Synergistic Treatment of Melanoma
In this study, we synthesized a molecule GA-1MT (GM) composed of indoleamine 2,3-dioxygenase (IDO) inhibitor (1-methyl-d-tryptophan, 1MT) called NLG8189 and gallic acid (GA) and verified its therapeutic effect on B16F10 melanoma cells and an orthotopic tumor-bearing mouse model. The synthesized mole...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-07-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.904229/full |
| _version_ | 1811325719138009088 |
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| author | Hongmei Liu Hongmei Liu Huan Gao Cheng Chen Wenyu Jia Delong Xu Guan Jiang Guan Jiang |
| author_facet | Hongmei Liu Hongmei Liu Huan Gao Cheng Chen Wenyu Jia Delong Xu Guan Jiang Guan Jiang |
| author_sort | Hongmei Liu |
| collection | DOAJ |
| description | In this study, we synthesized a molecule GA-1MT (GM) composed of indoleamine 2,3-dioxygenase (IDO) inhibitor (1-methyl-d-tryptophan, 1MT) called NLG8189 and gallic acid (GA) and verified its therapeutic effect on B16F10 melanoma cells and an orthotopic tumor-bearing mouse model. The synthesized molecule GM was analyzed by 1H NMR and mass spectrometry (MS). In addition, we confirmed that GM could mediate the immune response in the B16F10 cell tumor model by flow cytometry and immunofluorescence. The synthesized GM molecule could increase the solubility of 1MT to enhance the drug efficacy and lower costs. Moreover, GM could inhibit melanoma growth by combining 1MT and GA. In vivo experiments showed that GM could effectively inhibit the expression of tyrosinase, regulate the proportion of CD4+ T cells, CD8+ T cells, and regulatory T cells (Treg cells) in tumors, and significantly suppress melanoma growth. The newly synthesized drug GM could more effectively inhibit melanoma than GA and 1MT alone or in combination. |
| first_indexed | 2024-04-13T14:37:45Z |
| format | Article |
| id | doaj.art-4eecfc81116e44dbaadf8a7bc541b588 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-13T14:37:45Z |
| publishDate | 2022-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-4eecfc81116e44dbaadf8a7bc541b5882022-12-22T02:42:59ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-07-011210.3389/fonc.2022.904229904229IDO Inhibitor and Gallic Acid Cross-Linked Small Molecule Drug Synergistic Treatment of MelanomaHongmei Liu0Hongmei Liu1Huan Gao2Cheng Chen3Wenyu Jia4Delong Xu5Guan Jiang6Guan Jiang7Xuzhou Medical University, Xuzhou, ChinaDepartment of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, ChinaDepartment of Dermatology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, ChinaDepartment of Dermatology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, ChinaDepartment of Dermatology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, ChinaDepartment of Dermatology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, ChinaXuzhou Medical University, Xuzhou, ChinaDepartment of Dermatology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, ChinaIn this study, we synthesized a molecule GA-1MT (GM) composed of indoleamine 2,3-dioxygenase (IDO) inhibitor (1-methyl-d-tryptophan, 1MT) called NLG8189 and gallic acid (GA) and verified its therapeutic effect on B16F10 melanoma cells and an orthotopic tumor-bearing mouse model. The synthesized molecule GM was analyzed by 1H NMR and mass spectrometry (MS). In addition, we confirmed that GM could mediate the immune response in the B16F10 cell tumor model by flow cytometry and immunofluorescence. The synthesized GM molecule could increase the solubility of 1MT to enhance the drug efficacy and lower costs. Moreover, GM could inhibit melanoma growth by combining 1MT and GA. In vivo experiments showed that GM could effectively inhibit the expression of tyrosinase, regulate the proportion of CD4+ T cells, CD8+ T cells, and regulatory T cells (Treg cells) in tumors, and significantly suppress melanoma growth. The newly synthesized drug GM could more effectively inhibit melanoma than GA and 1MT alone or in combination.https://www.frontiersin.org/articles/10.3389/fonc.2022.904229/fullgallic acidindoleamine 23-dioxygenasemelanomachemotherapyimmunotherapy |
| spellingShingle | Hongmei Liu Hongmei Liu Huan Gao Cheng Chen Wenyu Jia Delong Xu Guan Jiang Guan Jiang IDO Inhibitor and Gallic Acid Cross-Linked Small Molecule Drug Synergistic Treatment of Melanoma Frontiers in Oncology gallic acid indoleamine 2 3-dioxygenase melanoma chemotherapy immunotherapy |
| title | IDO Inhibitor and Gallic Acid Cross-Linked Small Molecule Drug Synergistic Treatment of Melanoma |
| title_full | IDO Inhibitor and Gallic Acid Cross-Linked Small Molecule Drug Synergistic Treatment of Melanoma |
| title_fullStr | IDO Inhibitor and Gallic Acid Cross-Linked Small Molecule Drug Synergistic Treatment of Melanoma |
| title_full_unstemmed | IDO Inhibitor and Gallic Acid Cross-Linked Small Molecule Drug Synergistic Treatment of Melanoma |
| title_short | IDO Inhibitor and Gallic Acid Cross-Linked Small Molecule Drug Synergistic Treatment of Melanoma |
| title_sort | ido inhibitor and gallic acid cross linked small molecule drug synergistic treatment of melanoma |
| topic | gallic acid indoleamine 2 3-dioxygenase melanoma chemotherapy immunotherapy |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.904229/full |
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