Pterostilbene Enhances Cytotoxicity and Chemosensitivity in Human Pancreatic Cancer Cells
Gemcitabine (GEM) drug resistance causes high mortality rates and poor outcomes in pancreatic ductal adenocarcinoma (PDAC) patients. Receptor for advanced glycation end products (RAGE) involvement in the GEM resistance process has been demonstrated. Therefore, finding a safe and effective way to inh...
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| Language: | English |
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MDPI AG
2020-05-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/10/5/709 |
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| author | Yi-Hao Hsu Sheng-Yi Chen Sheng-Yang Wang Jer-An Lin Gow-Chin Yen |
| author_facet | Yi-Hao Hsu Sheng-Yi Chen Sheng-Yang Wang Jer-An Lin Gow-Chin Yen |
| author_sort | Yi-Hao Hsu |
| collection | DOAJ |
| description | Gemcitabine (GEM) drug resistance causes high mortality rates and poor outcomes in pancreatic ductal adenocarcinoma (PDAC) patients. Receptor for advanced glycation end products (RAGE) involvement in the GEM resistance process has been demonstrated. Therefore, finding a safe and effective way to inhibit receptors for RAGE-initiated GEM resistance is urgent. Pterostilbene (PTE), a natural methoxylated analogue derived from resveratrol and found in grapes and blueberries, has diverse bioactivities, such as antioxidative, anti-inflammatory, and anticancer qualities. The overall research objective was to determine the potential of PTE to enhance tumor cytotoxicity and chemosensitivity in PDAC cells. Our results have demonstrated that PTE induced S-phase cell cycle arrest, apoptosis, and autophagic cell death and inhibited multidrug resistance protein 1 (MDR1) expression by downregulating RAGE/PI3K/Akt signaling in both MIA PaCa-2 and MIA PaCa-2 <sup>GEMR</sup> cells (GEM-resistant cells). Remarkably, convincing evidence was established by RAGE small interfering RNA transfection. Taken together, our study demonstrated that PTE promoted chemosensitivity by inhibiting cell proliferation and MDR1 expression via the RAGE/PI3K/Akt axis in PDAC cells. The observations in these experiments indicate that PTE may play a crucial role in MDR1 modulation for PDAC treatment. |
| first_indexed | 2024-03-10T20:03:31Z |
| format | Article |
| id | doaj.art-5fd599c695f24c869fbbbf94683d0955 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T20:03:31Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-5fd599c695f24c869fbbbf94683d09552023-11-19T23:26:30ZengMDPI AGBiomolecules2218-273X2020-05-0110570910.3390/biom10050709Pterostilbene Enhances Cytotoxicity and Chemosensitivity in Human Pancreatic Cancer CellsYi-Hao Hsu0Sheng-Yi Chen1Sheng-Yang Wang2Jer-An Lin3Gow-Chin Yen4Department of Food Science and Biotechnology, National Chung Hsing University, 145 Xingda Road, Taichung 40227, TaiwanDepartment of Food Science and Biotechnology, National Chung Hsing University, 145 Xingda Road, Taichung 40227, TaiwanDepartment of Forestry, National Chung Hsing University, 145 Xingda Road, Taichung 40227, TaiwanGraduate Institute of Food Safety, National Chung Hsing University, 145 Xingda Road, Taichung 40227, TaiwanDepartment of Food Science and Biotechnology, National Chung Hsing University, 145 Xingda Road, Taichung 40227, TaiwanGemcitabine (GEM) drug resistance causes high mortality rates and poor outcomes in pancreatic ductal adenocarcinoma (PDAC) patients. Receptor for advanced glycation end products (RAGE) involvement in the GEM resistance process has been demonstrated. Therefore, finding a safe and effective way to inhibit receptors for RAGE-initiated GEM resistance is urgent. Pterostilbene (PTE), a natural methoxylated analogue derived from resveratrol and found in grapes and blueberries, has diverse bioactivities, such as antioxidative, anti-inflammatory, and anticancer qualities. The overall research objective was to determine the potential of PTE to enhance tumor cytotoxicity and chemosensitivity in PDAC cells. Our results have demonstrated that PTE induced S-phase cell cycle arrest, apoptosis, and autophagic cell death and inhibited multidrug resistance protein 1 (MDR1) expression by downregulating RAGE/PI3K/Akt signaling in both MIA PaCa-2 and MIA PaCa-2 <sup>GEMR</sup> cells (GEM-resistant cells). Remarkably, convincing evidence was established by RAGE small interfering RNA transfection. Taken together, our study demonstrated that PTE promoted chemosensitivity by inhibiting cell proliferation and MDR1 expression via the RAGE/PI3K/Akt axis in PDAC cells. The observations in these experiments indicate that PTE may play a crucial role in MDR1 modulation for PDAC treatment.https://www.mdpi.com/2218-273X/10/5/709apoptosisautophagychemosensitivitygemcitabinepancreatic ductal adenocarcinomapterostilbene |
| spellingShingle | Yi-Hao Hsu Sheng-Yi Chen Sheng-Yang Wang Jer-An Lin Gow-Chin Yen Pterostilbene Enhances Cytotoxicity and Chemosensitivity in Human Pancreatic Cancer Cells Biomolecules apoptosis autophagy chemosensitivity gemcitabine pancreatic ductal adenocarcinoma pterostilbene |
| title | Pterostilbene Enhances Cytotoxicity and Chemosensitivity in Human Pancreatic Cancer Cells |
| title_full | Pterostilbene Enhances Cytotoxicity and Chemosensitivity in Human Pancreatic Cancer Cells |
| title_fullStr | Pterostilbene Enhances Cytotoxicity and Chemosensitivity in Human Pancreatic Cancer Cells |
| title_full_unstemmed | Pterostilbene Enhances Cytotoxicity and Chemosensitivity in Human Pancreatic Cancer Cells |
| title_short | Pterostilbene Enhances Cytotoxicity and Chemosensitivity in Human Pancreatic Cancer Cells |
| title_sort | pterostilbene enhances cytotoxicity and chemosensitivity in human pancreatic cancer cells |
| topic | apoptosis autophagy chemosensitivity gemcitabine pancreatic ductal adenocarcinoma pterostilbene |
| url | https://www.mdpi.com/2218-273X/10/5/709 |
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