The Case for GNMT as a Biomarker and a Therapeutic Target in Pancreatic Cancer
The high mortality rate for pancreatic cancer (PC) is due to the lack of specific symptoms at early tumor stages and a high biological aggressiveness. Reliable biomarkers and new therapeutic targets would help to improve outlook in PC. In this study, we analyzed the expression of GNMT in a panel of...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-03-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/14/3/209 |
| _version_ | 1797415511199318016 |
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| author | Zachary Heinzman Connor Schmidt Marek K. Sliwinski Nalin C. W. Goonesekere |
| author_facet | Zachary Heinzman Connor Schmidt Marek K. Sliwinski Nalin C. W. Goonesekere |
| author_sort | Zachary Heinzman |
| collection | DOAJ |
| description | The high mortality rate for pancreatic cancer (PC) is due to the lack of specific symptoms at early tumor stages and a high biological aggressiveness. Reliable biomarkers and new therapeutic targets would help to improve outlook in PC. In this study, we analyzed the expression of GNMT in a panel of pancreatic cancer cell lines and in early-stage paired patient tissue samples (normal and diseased) by quantitative reverse transcription-PCR (qRT-PCR). We also investigated the effect of 1,2,3,4,6-penta-<i>O</i>-galloyl-β-<span style="font-variant: small-caps;">d</span>-glucopyranoside (PGG) as a therapeutic agent for PC. We find that GNMT is markedly downregulated (<i>p</i> < 0.05), in a majority of PC cell lines. Similar results are observed in early-stage patient tissue samples, where GNMT expression can be reduced by a 100-fold or more. We also show that PGG is a strong inhibitor of PC cell proliferation, with an IC<sub>50</sub> value of 12 ng/mL, and PGG upregulates GNMT expression in a dose-dependent manner. In conclusion, our data show that GNMT has promise as a biomarker and as a therapeutic target for PC. |
| first_indexed | 2024-03-09T05:48:39Z |
| format | Article |
| id | doaj.art-ee24363897204b5fa3c0f54d0acf71aa |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-09T05:48:39Z |
| publishDate | 2021-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-ee24363897204b5fa3c0f54d0acf71aa2023-12-03T12:19:20ZengMDPI AGPharmaceuticals1424-82472021-03-0114320910.3390/ph14030209The Case for GNMT as a Biomarker and a Therapeutic Target in Pancreatic CancerZachary Heinzman0Connor Schmidt1Marek K. Sliwinski2Nalin C. W. Goonesekere3Department of Chemistry and Biochemistry, University of Northern Iowa, Cedar Falls, IA 50614, USADepartment of Chemistry and Biochemistry, University of Northern Iowa, Cedar Falls, IA 50614, USADepartment of Biology, University of Northern Iowa, Cedar Falls, IA 50614, USADepartment of Chemistry and Biochemistry, University of Northern Iowa, Cedar Falls, IA 50614, USAThe high mortality rate for pancreatic cancer (PC) is due to the lack of specific symptoms at early tumor stages and a high biological aggressiveness. Reliable biomarkers and new therapeutic targets would help to improve outlook in PC. In this study, we analyzed the expression of GNMT in a panel of pancreatic cancer cell lines and in early-stage paired patient tissue samples (normal and diseased) by quantitative reverse transcription-PCR (qRT-PCR). We also investigated the effect of 1,2,3,4,6-penta-<i>O</i>-galloyl-β-<span style="font-variant: small-caps;">d</span>-glucopyranoside (PGG) as a therapeutic agent for PC. We find that GNMT is markedly downregulated (<i>p</i> < 0.05), in a majority of PC cell lines. Similar results are observed in early-stage patient tissue samples, where GNMT expression can be reduced by a 100-fold or more. We also show that PGG is a strong inhibitor of PC cell proliferation, with an IC<sub>50</sub> value of 12 ng/mL, and PGG upregulates GNMT expression in a dose-dependent manner. In conclusion, our data show that GNMT has promise as a biomarker and as a therapeutic target for PC.https://www.mdpi.com/1424-8247/14/3/209pancreatic cancerbiomarkerGNMT1,2,3,4,6-penta-<i>O</i>-galloyl-β-<span style="font-variant: small-caps">d</span>-glucopyranoside |
| spellingShingle | Zachary Heinzman Connor Schmidt Marek K. Sliwinski Nalin C. W. Goonesekere The Case for GNMT as a Biomarker and a Therapeutic Target in Pancreatic Cancer Pharmaceuticals pancreatic cancer biomarker GNMT 1,2,3,4,6-penta-<i>O</i>-galloyl-β-<span style="font-variant: small-caps">d</span>-glucopyranoside |
| title | The Case for GNMT as a Biomarker and a Therapeutic Target in Pancreatic Cancer |
| title_full | The Case for GNMT as a Biomarker and a Therapeutic Target in Pancreatic Cancer |
| title_fullStr | The Case for GNMT as a Biomarker and a Therapeutic Target in Pancreatic Cancer |
| title_full_unstemmed | The Case for GNMT as a Biomarker and a Therapeutic Target in Pancreatic Cancer |
| title_short | The Case for GNMT as a Biomarker and a Therapeutic Target in Pancreatic Cancer |
| title_sort | case for gnmt as a biomarker and a therapeutic target in pancreatic cancer |
| topic | pancreatic cancer biomarker GNMT 1,2,3,4,6-penta-<i>O</i>-galloyl-β-<span style="font-variant: small-caps">d</span>-glucopyranoside |
| url | https://www.mdpi.com/1424-8247/14/3/209 |
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