The Novel Antitumor Compound HCA Promotes Glioma Cell Death by Inducing Endoplasmic Reticulum Stress and Autophagy
Glioblastoma (GBM) is the most common and aggressive type of primary brain tumor in adults, and the median survival of patients with GBM is 14.5 months. Melitherapy is an innovative therapeutic approach to treat different diseases, including cancer, and it is based on the regulation of cell membrane...
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| Format: | Article |
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MDPI AG
2021-08-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/17/4290 |
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| author | Roberto Beteta-Göbel Javier Fernández-Díaz Laura Arbona-González Raquel Rodríguez-Lorca Manuel Torres Xavier Busquets Paula Fernández-García Pablo V. Escribá Victoria Lladó |
| author_facet | Roberto Beteta-Göbel Javier Fernández-Díaz Laura Arbona-González Raquel Rodríguez-Lorca Manuel Torres Xavier Busquets Paula Fernández-García Pablo V. Escribá Victoria Lladó |
| author_sort | Roberto Beteta-Göbel |
| collection | DOAJ |
| description | Glioblastoma (GBM) is the most common and aggressive type of primary brain tumor in adults, and the median survival of patients with GBM is 14.5 months. Melitherapy is an innovative therapeutic approach to treat different diseases, including cancer, and it is based on the regulation of cell membrane composition and structure, which modulates relevant signal pathways. Here, we have tested the effects of 2-hydroxycervonic acid (HCA) on GBM cells and xenograft tumors. HCA was taken up by cells and it compromised the survival of several human GBM cell lines in vitro, as well as the in vivo growth of xenograft tumors (mice) derived from these cells. HCA appeared to enhance ER stress/UPR signaling, which consequently induced autophagic cell death of the GBM tumor cells. This negative effect of HCA on GBM cells may be mediated by the JNK/c-Jun/CHOP/BiP axis, and it also seems to be provoked by the cellular metabolite of HCA, C21:5n-3 (heneicosapentaenoic acid). These results demonstrate the efficacy of the melitherapeutic treatment used and the potential of using C21:5n-3 as an efficacy biomarker for this treatment. Given the safety profile in animal models, the data presented here provide evidence that HCA warrants further clinical study as a potential therapy for GBM, currently an important unmet medical need. |
| first_indexed | 2024-03-10T08:14:59Z |
| format | Article |
| id | doaj.art-c3ac48ad66c141f486aea57da3d2f8ff |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T08:14:59Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-c3ac48ad66c141f486aea57da3d2f8ff2023-11-22T10:25:08ZengMDPI AGCancers2072-66942021-08-011317429010.3390/cancers13174290The Novel Antitumor Compound HCA Promotes Glioma Cell Death by Inducing Endoplasmic Reticulum Stress and AutophagyRoberto Beteta-Göbel0Javier Fernández-Díaz1Laura Arbona-González2Raquel Rodríguez-Lorca3Manuel Torres4Xavier Busquets5Paula Fernández-García6Pablo V. Escribá7Victoria Lladó8Laboratory 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, SpainDepartment of R&D, Laminar Pharmaceuticals, Isaac Newton, 07121 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, SpainGlioblastoma (GBM) is the most common and aggressive type of primary brain tumor in adults, and the median survival of patients with GBM is 14.5 months. Melitherapy is an innovative therapeutic approach to treat different diseases, including cancer, and it is based on the regulation of cell membrane composition and structure, which modulates relevant signal pathways. Here, we have tested the effects of 2-hydroxycervonic acid (HCA) on GBM cells and xenograft tumors. HCA was taken up by cells and it compromised the survival of several human GBM cell lines in vitro, as well as the in vivo growth of xenograft tumors (mice) derived from these cells. HCA appeared to enhance ER stress/UPR signaling, which consequently induced autophagic cell death of the GBM tumor cells. This negative effect of HCA on GBM cells may be mediated by the JNK/c-Jun/CHOP/BiP axis, and it also seems to be provoked by the cellular metabolite of HCA, C21:5n-3 (heneicosapentaenoic acid). These results demonstrate the efficacy of the melitherapeutic treatment used and the potential of using C21:5n-3 as an efficacy biomarker for this treatment. Given the safety profile in animal models, the data presented here provide evidence that HCA warrants further clinical study as a potential therapy for GBM, currently an important unmet medical need.https://www.mdpi.com/2072-6694/13/17/4290HCAmembrane lipid therapygliomaER stressautophagy |
| spellingShingle | Roberto Beteta-Göbel Javier Fernández-Díaz Laura Arbona-González Raquel Rodríguez-Lorca Manuel Torres Xavier Busquets Paula Fernández-García Pablo V. Escribá Victoria Lladó The Novel Antitumor Compound HCA Promotes Glioma Cell Death by Inducing Endoplasmic Reticulum Stress and Autophagy Cancers HCA membrane lipid therapy glioma ER stress autophagy |
| title | The Novel Antitumor Compound HCA Promotes Glioma Cell Death by Inducing Endoplasmic Reticulum Stress and Autophagy |
| title_full | The Novel Antitumor Compound HCA Promotes Glioma Cell Death by Inducing Endoplasmic Reticulum Stress and Autophagy |
| title_fullStr | The Novel Antitumor Compound HCA Promotes Glioma Cell Death by Inducing Endoplasmic Reticulum Stress and Autophagy |
| title_full_unstemmed | The Novel Antitumor Compound HCA Promotes Glioma Cell Death by Inducing Endoplasmic Reticulum Stress and Autophagy |
| title_short | The Novel Antitumor Compound HCA Promotes Glioma Cell Death by Inducing Endoplasmic Reticulum Stress and Autophagy |
| title_sort | novel antitumor compound hca promotes glioma cell death by inducing endoplasmic reticulum stress and autophagy |
| topic | HCA membrane lipid therapy glioma ER stress autophagy |
| url | https://www.mdpi.com/2072-6694/13/17/4290 |
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