HCA (2-Hydroxy-Docosahexaenoic Acid) Induces Apoptosis and Endoplasmic Reticulum Stress in Pancreatic Cancer Cells
Pancreatic cancer has a high mortality rate due to its aggressive nature and high metastatic rate. When coupled to the difficulties in detecting this type of tumor early and the lack of effective treatments, this cancer is currently one of the most important clinical challenges in the field of oncol...
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MDPI AG
2022-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/17/9902 |
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| author | Roberto Beteta-Göbel Marc Miralles Javier Fernández-Díaz Raquel Rodríguez-Lorca Manuel Torres Paula Fernández-García Pablo V. Escribá Victoria Lladó |
| author_facet | Roberto Beteta-Göbel Marc Miralles Javier Fernández-Díaz Raquel Rodríguez-Lorca Manuel Torres Paula Fernández-García Pablo V. Escribá Victoria Lladó |
| author_sort | Roberto Beteta-Göbel |
| collection | DOAJ |
| description | Pancreatic cancer has a high mortality rate due to its aggressive nature and high metastatic rate. When coupled to the difficulties in detecting this type of tumor early and the lack of effective treatments, this cancer is currently one of the most important clinical challenges in the field of oncology. Melitherapy is an innovative therapeutic approach that is based on modifying the composition and structure of cell membranes to treat different diseases, including cancers. In this context, 2-hydroxycervonic acid (HCA) is a melitherapeutic agent developed to combat pancreatic cancer cells, provoking the programmed cell death by apoptosis of these cells by inducing ER stress and triggering the production of ROS species. The efficacy of HCA was demonstrated in vivo, alone and in combination with gemcitabine, using a MIA PaCa-2 cell xenograft model of pancreatic cancer in which no apparent toxicity was evident. HCA is metabolized by α-oxidation to C21:5n-3 (heneicosapentaenoic acid), which in turn also showed anti-proliferative effect in these cells. Given the unmet clinical needs associated with pancreatic cancer, the data presented here suggest that the use of HCA merits further study as a potential therapy for this condition. |
| first_indexed | 2024-03-10T01:43:19Z |
| format | Article |
| id | doaj.art-6cd240aee00e49fcaf9a7b4715d5f7df |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T01:43:19Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-6cd240aee00e49fcaf9a7b4715d5f7df2023-11-23T13:19:09ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-08-012317990210.3390/ijms23179902HCA (2-Hydroxy-Docosahexaenoic Acid) Induces Apoptosis and Endoplasmic Reticulum Stress in Pancreatic Cancer CellsRoberto Beteta-Göbel0Marc Miralles1Javier Fernández-Díaz2Raquel Rodríguez-Lorca3Manuel Torres4Paula Fernández-García5Pablo V. Escribá6Victoria Lladó7Laboratory of Molecular Cell Biomedicine, Department of Biology, University of the Balearic Islands, 07122 Palma de Mallorca, SpainLaboratory of Molecular Cell Biomedicine, Department of Biology, University of the Balearic Islands, 07122 Palma de Mallorca, SpainLaboratory of Molecular Cell Biomedicine, Department of Biology, University of the Balearic Islands, 07122 Palma de Mallorca, SpainLaboratory of Molecular Cell Biomedicine, Department of Biology, University of the Balearic Islands, 07122 Palma de Mallorca, SpainLaboratory of Molecular Cell Biomedicine, Department of Biology, University of the Balearic Islands, 07122 Palma de Mallorca, SpainLaboratory of Molecular Cell Biomedicine, Department of Biology, University of the Balearic Islands, 07122 Palma de Mallorca, SpainLaboratory of Molecular Cell Biomedicine, Department of Biology, University of the Balearic Islands, 07122 Palma de Mallorca, SpainLaboratory of Molecular Cell Biomedicine, Department of Biology, University of the Balearic Islands, 07122 Palma de Mallorca, SpainPancreatic cancer has a high mortality rate due to its aggressive nature and high metastatic rate. When coupled to the difficulties in detecting this type of tumor early and the lack of effective treatments, this cancer is currently one of the most important clinical challenges in the field of oncology. Melitherapy is an innovative therapeutic approach that is based on modifying the composition and structure of cell membranes to treat different diseases, including cancers. In this context, 2-hydroxycervonic acid (HCA) is a melitherapeutic agent developed to combat pancreatic cancer cells, provoking the programmed cell death by apoptosis of these cells by inducing ER stress and triggering the production of ROS species. The efficacy of HCA was demonstrated in vivo, alone and in combination with gemcitabine, using a MIA PaCa-2 cell xenograft model of pancreatic cancer in which no apparent toxicity was evident. HCA is metabolized by α-oxidation to C21:5n-3 (heneicosapentaenoic acid), which in turn also showed anti-proliferative effect in these cells. Given the unmet clinical needs associated with pancreatic cancer, the data presented here suggest that the use of HCA merits further study as a potential therapy for this condition.https://www.mdpi.com/1422-0067/23/17/9902HCAmembrane lipid therapypancreatic cancerapoptosisER stress |
| spellingShingle | Roberto Beteta-Göbel Marc Miralles Javier Fernández-Díaz Raquel Rodríguez-Lorca Manuel Torres Paula Fernández-García Pablo V. Escribá Victoria Lladó HCA (2-Hydroxy-Docosahexaenoic Acid) Induces Apoptosis and Endoplasmic Reticulum Stress in Pancreatic Cancer Cells International Journal of Molecular Sciences HCA membrane lipid therapy pancreatic cancer apoptosis ER stress |
| title | HCA (2-Hydroxy-Docosahexaenoic Acid) Induces Apoptosis and Endoplasmic Reticulum Stress in Pancreatic Cancer Cells |
| title_full | HCA (2-Hydroxy-Docosahexaenoic Acid) Induces Apoptosis and Endoplasmic Reticulum Stress in Pancreatic Cancer Cells |
| title_fullStr | HCA (2-Hydroxy-Docosahexaenoic Acid) Induces Apoptosis and Endoplasmic Reticulum Stress in Pancreatic Cancer Cells |
| title_full_unstemmed | HCA (2-Hydroxy-Docosahexaenoic Acid) Induces Apoptosis and Endoplasmic Reticulum Stress in Pancreatic Cancer Cells |
| title_short | HCA (2-Hydroxy-Docosahexaenoic Acid) Induces Apoptosis and Endoplasmic Reticulum Stress in Pancreatic Cancer Cells |
| title_sort | hca 2 hydroxy docosahexaenoic acid induces apoptosis and endoplasmic reticulum stress in pancreatic cancer cells |
| topic | HCA membrane lipid therapy pancreatic cancer apoptosis ER stress |
| url | https://www.mdpi.com/1422-0067/23/17/9902 |
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