A Theoretical Study on the Efficacy and Mechanism of Combined YAP-1 and PARP-1 Inhibitors in the Treatment of Glioblastoma Multiforme Using Peruvian Maca <i>Lepidium meyenii</i>
Glioblastoma multiforme (GBM) is one of the most aggressive and treatment-resistant forms of brain cancer. Current therapeutic strategies, including surgery, chemotherapy, and radiotherapy, often fail due to the tumor’s ability to develop resistance. The proteins YAP-1 (Yes-associated protein 1) and...
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2025-01-01
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| author | Albert Gabriel Turpo-Peqqueña Sebastian Luna-Prado Renato Javier Valencia-Arce Fabio Leonardo Del-Carpio-Carrazco Badhin Gómez |
| author_facet | Albert Gabriel Turpo-Peqqueña Sebastian Luna-Prado Renato Javier Valencia-Arce Fabio Leonardo Del-Carpio-Carrazco Badhin Gómez |
| author_sort | Albert Gabriel Turpo-Peqqueña |
| collection | DOAJ |
| description | Glioblastoma multiforme (GBM) is one of the most aggressive and treatment-resistant forms of brain cancer. Current therapeutic strategies, including surgery, chemotherapy, and radiotherapy, often fail due to the tumor’s ability to develop resistance. The proteins YAP-1 (Yes-associated protein 1) and PARP-1 (Poly-(ADP-ribose)–polymerase-1) have been implicated in this resistance, playing crucial roles in cell proliferation and DNA repair mechanisms, respectively. This study explored the inhibitory potential of natural compounds from <i>Lepidium meyenii</i> (Peruvian Maca) on the YAP-1 and PARP-1 protein systems to develop novel therapeutic strategies for GBM. By molecular dynamics simulations, we identified N-(3-Methoxybenzyl)-(9Z,12Z,15Z)- octadecatrienamide (DK5) as the most promising natural inhibitor for PARP-1 and stearic acid (GK4) for YAP-1. Although synthetic inhibitors, such as Olaparib (ODK) for PARP-1 and Verteporfin (VER) for YAP-1, only VER was superior to the naturally occurring molecule and proved a promising alternative. In conclusion, natural compounds from <i>Lepidium meyenii</i> (Peruvian Maca) offer a potentially innovative approach to improve GBM treatment, complementing existing therapies with their inhibitory action on PARP-1 and YAP-1. |
| format | Article |
| id | doaj-art-321d8727a97f423bb8434105fc01ce1f |
| institution | Kabale University |
| issn | 1467-3037 1467-3045 |
| language | English |
| publishDate | 2025-01-01 |
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| series | Current Issues in Molecular Biology |
| spelling | doaj-art-321d8727a97f423bb8434105fc01ce1f2025-01-24T13:27:30ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452025-01-014714010.3390/cimb47010040A Theoretical Study on the Efficacy and Mechanism of Combined YAP-1 and PARP-1 Inhibitors in the Treatment of Glioblastoma Multiforme Using Peruvian Maca <i>Lepidium meyenii</i>Albert Gabriel Turpo-Peqqueña0Sebastian Luna-Prado1Renato Javier Valencia-Arce2Fabio Leonardo Del-Carpio-Carrazco3Badhin Gómez4Centro de Investigación en Ingeniería Molecular–CIIM, Universidad Católica de Santa María, Urb. San José s/n, Umacollo, Arequipa 04013, PeruCentro de Investigación en Ingeniería Molecular–CIIM, Universidad Católica de Santa María, Urb. San José s/n, Umacollo, Arequipa 04013, PeruCentro de Investigación en Ingeniería Molecular–CIIM, Universidad Católica de Santa María, Urb. San José s/n, Umacollo, Arequipa 04013, PeruCentro de Investigación en Ingeniería Molecular–CIIM, Universidad Católica de Santa María, Urb. San José s/n, Umacollo, Arequipa 04013, PeruCentro de Investigación en Ingeniería Molecular–CIIM, Universidad Católica de Santa María, Urb. San José s/n, Umacollo, Arequipa 04013, PeruGlioblastoma multiforme (GBM) is one of the most aggressive and treatment-resistant forms of brain cancer. Current therapeutic strategies, including surgery, chemotherapy, and radiotherapy, often fail due to the tumor’s ability to develop resistance. The proteins YAP-1 (Yes-associated protein 1) and PARP-1 (Poly-(ADP-ribose)–polymerase-1) have been implicated in this resistance, playing crucial roles in cell proliferation and DNA repair mechanisms, respectively. This study explored the inhibitory potential of natural compounds from <i>Lepidium meyenii</i> (Peruvian Maca) on the YAP-1 and PARP-1 protein systems to develop novel therapeutic strategies for GBM. By molecular dynamics simulations, we identified N-(3-Methoxybenzyl)-(9Z,12Z,15Z)- octadecatrienamide (DK5) as the most promising natural inhibitor for PARP-1 and stearic acid (GK4) for YAP-1. Although synthetic inhibitors, such as Olaparib (ODK) for PARP-1 and Verteporfin (VER) for YAP-1, only VER was superior to the naturally occurring molecule and proved a promising alternative. In conclusion, natural compounds from <i>Lepidium meyenii</i> (Peruvian Maca) offer a potentially innovative approach to improve GBM treatment, complementing existing therapies with their inhibitory action on PARP-1 and YAP-1.https://www.mdpi.com/1467-3045/47/1/40glioblastoma multiformeNeuro-oncologyNeurosurgeryMolecular Mechanicsmolecular dockingmolecular dynamics simulation |
| spellingShingle | Albert Gabriel Turpo-Peqqueña Sebastian Luna-Prado Renato Javier Valencia-Arce Fabio Leonardo Del-Carpio-Carrazco Badhin Gómez A Theoretical Study on the Efficacy and Mechanism of Combined YAP-1 and PARP-1 Inhibitors in the Treatment of Glioblastoma Multiforme Using Peruvian Maca <i>Lepidium meyenii</i> Current Issues in Molecular Biology glioblastoma multiforme Neuro-oncology Neurosurgery Molecular Mechanics molecular docking molecular dynamics simulation |
| title | A Theoretical Study on the Efficacy and Mechanism of Combined YAP-1 and PARP-1 Inhibitors in the Treatment of Glioblastoma Multiforme Using Peruvian Maca <i>Lepidium meyenii</i> |
| title_full | A Theoretical Study on the Efficacy and Mechanism of Combined YAP-1 and PARP-1 Inhibitors in the Treatment of Glioblastoma Multiforme Using Peruvian Maca <i>Lepidium meyenii</i> |
| title_fullStr | A Theoretical Study on the Efficacy and Mechanism of Combined YAP-1 and PARP-1 Inhibitors in the Treatment of Glioblastoma Multiforme Using Peruvian Maca <i>Lepidium meyenii</i> |
| title_full_unstemmed | A Theoretical Study on the Efficacy and Mechanism of Combined YAP-1 and PARP-1 Inhibitors in the Treatment of Glioblastoma Multiforme Using Peruvian Maca <i>Lepidium meyenii</i> |
| title_short | A Theoretical Study on the Efficacy and Mechanism of Combined YAP-1 and PARP-1 Inhibitors in the Treatment of Glioblastoma Multiforme Using Peruvian Maca <i>Lepidium meyenii</i> |
| title_sort | theoretical study on the efficacy and mechanism of combined yap 1 and parp 1 inhibitors in the treatment of glioblastoma multiforme using peruvian maca i lepidium meyenii i |
| topic | glioblastoma multiforme Neuro-oncology Neurosurgery Molecular Mechanics molecular docking molecular dynamics simulation |
| url | https://www.mdpi.com/1467-3045/47/1/40 |
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