New Marine Fungal Deoxy-14,15-Dehydroisoaustamide Resensitizes Prostate Cancer Cells to Enzalutamide
Marine fungi serve as a valuable source for new bioactive molecules bearing various biological activities. In this study, we report on the isolation of a new indole diketopiperazine alkaloid deoxy-14,15-dehydroisoaustamide (<b>1</b>) from the marine-derived fungus <i>Penicillium di...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-01-01
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| Series: | Marine Drugs |
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| Online Access: | https://www.mdpi.com/1660-3397/21/1/54 |
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| author | Sergey A. Dyshlovoy Olesya I. Zhuravleva Jessica Hauschild Tobias Busenbender Dmitry N. Pelageev Anton N. Yurchenko Yuliya V. Khudyakova Alexandr S. Antonov Markus Graefen Carsten Bokemeyer Gunhild von Amsberg |
| author_facet | Sergey A. Dyshlovoy Olesya I. Zhuravleva Jessica Hauschild Tobias Busenbender Dmitry N. Pelageev Anton N. Yurchenko Yuliya V. Khudyakova Alexandr S. Antonov Markus Graefen Carsten Bokemeyer Gunhild von Amsberg |
| author_sort | Sergey A. Dyshlovoy |
| collection | DOAJ |
| description | Marine fungi serve as a valuable source for new bioactive molecules bearing various biological activities. In this study, we report on the isolation of a new indole diketopiperazine alkaloid deoxy-14,15-dehydroisoaustamide (<b>1</b>) from the marine-derived fungus <i>Penicillium dimorphosporum</i> KMM 4689 associated with a soft coral. The structure of this metabolite, including its absolute configuration, was determined by HR-MS, 1D and 2D NMR as well as CD data. Compound <b>1</b> is a very first deoxyisoaustamide alkaloid possessing two double bonds in the proline ring. The isolated compound was noncytotoxic to a panel of human normal and cancer cell lines up to 100 µM. At the same time, compound <b>1</b> resensitized prostate cancer 22Rv1 cells to androgen receptor (AR) blocker enzalutamide. The mechanism of this phenomenon was identified as specific drug-induced degradation of androgen receptor transcription variant V7 (AR-V7), which also resulted in general suppression of AR signaling. Our data suggest that the isolated alkaloid is a promising candidate for combinational therapy of castration resistant prostate cancer, including drug-resistant subtypes. |
| first_indexed | 2024-03-09T11:52:04Z |
| format | Article |
| id | doaj.art-045b1ac7fd144b5f833a4e57488d6c26 |
| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-03-09T11:52:04Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-045b1ac7fd144b5f833a4e57488d6c262023-11-30T23:13:54ZengMDPI AGMarine Drugs1660-33972023-01-012115410.3390/md21010054New Marine Fungal Deoxy-14,15-Dehydroisoaustamide Resensitizes Prostate Cancer Cells to EnzalutamideSergey A. Dyshlovoy0Olesya I. Zhuravleva1Jessica Hauschild2Tobias Busenbender3Dmitry N. Pelageev4Anton N. Yurchenko5Yuliya V. Khudyakova6Alexandr S. Antonov7Markus Graefen8Carsten Bokemeyer9Gunhild von Amsberg10Laboratory of Experimental Oncology, Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald-Tumorzentrum—University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, 20246 Hamburg, GermanyInstitute of High Technologies and Advanced Materials, Far Eastern Federal University, Vladivostok 690922, RussiaLaboratory of Experimental Oncology, Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald-Tumorzentrum—University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, 20246 Hamburg, GermanyLaboratory of Experimental Oncology, Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald-Tumorzentrum—University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, 20246 Hamburg, GermanyG.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of the Russian Academy of Sciences, Prospect 100-Letiya Vladivostoka, Vladivostok 690022, RussiaG.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of the Russian Academy of Sciences, Prospect 100-Letiya Vladivostoka, Vladivostok 690022, RussiaG.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of the Russian Academy of Sciences, Prospect 100-Letiya Vladivostoka, Vladivostok 690022, RussiaG.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of the Russian Academy of Sciences, Prospect 100-Letiya Vladivostoka, Vladivostok 690022, RussiaMartini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, 20246 Hamburg, GermanyLaboratory of Experimental Oncology, Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald-Tumorzentrum—University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, 20246 Hamburg, GermanyLaboratory of Experimental Oncology, Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald-Tumorzentrum—University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, 20246 Hamburg, GermanyMarine fungi serve as a valuable source for new bioactive molecules bearing various biological activities. In this study, we report on the isolation of a new indole diketopiperazine alkaloid deoxy-14,15-dehydroisoaustamide (<b>1</b>) from the marine-derived fungus <i>Penicillium dimorphosporum</i> KMM 4689 associated with a soft coral. The structure of this metabolite, including its absolute configuration, was determined by HR-MS, 1D and 2D NMR as well as CD data. Compound <b>1</b> is a very first deoxyisoaustamide alkaloid possessing two double bonds in the proline ring. The isolated compound was noncytotoxic to a panel of human normal and cancer cell lines up to 100 µM. At the same time, compound <b>1</b> resensitized prostate cancer 22Rv1 cells to androgen receptor (AR) blocker enzalutamide. The mechanism of this phenomenon was identified as specific drug-induced degradation of androgen receptor transcription variant V7 (AR-V7), which also resulted in general suppression of AR signaling. Our data suggest that the isolated alkaloid is a promising candidate for combinational therapy of castration resistant prostate cancer, including drug-resistant subtypes.https://www.mdpi.com/1660-3397/21/1/54<i>Penicillium dimorphosporum</i>secondary metabolitesprenylated indole alkaloidprostate cancerandrogen receptorenzalutamide |
| spellingShingle | Sergey A. Dyshlovoy Olesya I. Zhuravleva Jessica Hauschild Tobias Busenbender Dmitry N. Pelageev Anton N. Yurchenko Yuliya V. Khudyakova Alexandr S. Antonov Markus Graefen Carsten Bokemeyer Gunhild von Amsberg New Marine Fungal Deoxy-14,15-Dehydroisoaustamide Resensitizes Prostate Cancer Cells to Enzalutamide Marine Drugs <i>Penicillium dimorphosporum</i> secondary metabolites prenylated indole alkaloid prostate cancer androgen receptor enzalutamide |
| title | New Marine Fungal Deoxy-14,15-Dehydroisoaustamide Resensitizes Prostate Cancer Cells to Enzalutamide |
| title_full | New Marine Fungal Deoxy-14,15-Dehydroisoaustamide Resensitizes Prostate Cancer Cells to Enzalutamide |
| title_fullStr | New Marine Fungal Deoxy-14,15-Dehydroisoaustamide Resensitizes Prostate Cancer Cells to Enzalutamide |
| title_full_unstemmed | New Marine Fungal Deoxy-14,15-Dehydroisoaustamide Resensitizes Prostate Cancer Cells to Enzalutamide |
| title_short | New Marine Fungal Deoxy-14,15-Dehydroisoaustamide Resensitizes Prostate Cancer Cells to Enzalutamide |
| title_sort | new marine fungal deoxy 14 15 dehydroisoaustamide resensitizes prostate cancer cells to enzalutamide |
| topic | <i>Penicillium dimorphosporum</i> secondary metabolites prenylated indole alkaloid prostate cancer androgen receptor enzalutamide |
| url | https://www.mdpi.com/1660-3397/21/1/54 |
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