Open Access
Marine Drugs, volume 21, issue 1, pages 54
New Marine Fungal Deoxy-14,15-Dehydroisoaustamide Resensitizes Prostate Cancer Cells to Enzalutamide
Dyshlovoy Sergey A.
1, 2
,
Zhuravleva Olesya I
2, 3
,
Hauschild Jessica
1
,
Busenbender Tobias
1
,
Khudyakova Yuliya V
3
,
Antonov Alexandr S.
3
,
Graefen Markus
4
,
von Amsberg Gunhild
1, 4
1
Laboratory 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, Germany
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4
Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, 20246 Hamburg, Germany
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Publication type: Journal Article
Publication date: 2023-01-14
PubMed ID:
36662227
Drug Discovery
Pharmaceutical Science
Pharmacology, Toxicology and Pharmaceutics (miscellaneous)
Abstract
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 (1) from the marine-derived fungus Penicillium dimorphosporum 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 1 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 1 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.
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Fermentation
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Fermentation
1 publication, 100%
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Multidisciplinary Digital Publishing Institute (MDPI)
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Multidisciplinary Digital Publishing Institute (MDPI)
1 publication, 100%
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Dyshlovoy S. A. et al. New Marine Fungal Deoxy-14,15-Dehydroisoaustamide Resensitizes Prostate Cancer Cells to Enzalutamide // Marine Drugs. 2023. Vol. 21. No. 1. p. 54.
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Dyshlovoy S. A., Zhuravleva O. I., Hauschild J., Busenbender T., Pelageev D. N., Yurchenko A. N., Khudyakova Y. V., Antonov A. S., Graefen M., Bokemeyer C., von Amsberg G. New Marine Fungal Deoxy-14,15-Dehydroisoaustamide Resensitizes Prostate Cancer Cells to Enzalutamide // Marine Drugs. 2023. Vol. 21. No. 1. p. 54.
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TY - JOUR
DO - 10.3390/md21010054
UR - https://doi.org/10.3390%2Fmd21010054
TI - New Marine Fungal Deoxy-14,15-Dehydroisoaustamide Resensitizes Prostate Cancer Cells to Enzalutamide
T2 - Marine Drugs
AU - Dyshlovoy, Sergey A.
AU - Zhuravleva, Olesya I
AU - Hauschild, Jessica
AU - Busenbender, Tobias
AU - Pelageev, Dmitry N
AU - Yurchenko, Anton N
AU - Khudyakova, Yuliya V
AU - Antonov, Alexandr S.
AU - Graefen, Markus
AU - Bokemeyer, Carsten
AU - von Amsberg, Gunhild
PY - 2023
DA - 2023/01/14 00:00:00
PB - Multidisciplinary Digital Publishing Institute (MDPI)
SP - 54
IS - 1
VL - 21
PMID - 36662227
SN - 1660-3397
ER -
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@article{2023_Dyshlovoy,
author = {Sergey A. Dyshlovoy and Olesya I Zhuravleva and Jessica Hauschild and Tobias Busenbender and Dmitry N Pelageev and Anton N Yurchenko and Yuliya V Khudyakova and Alexandr S. Antonov and Markus Graefen and Carsten Bokemeyer and Gunhild von Amsberg},
title = {New Marine Fungal Deoxy-14,15-Dehydroisoaustamide Resensitizes Prostate Cancer Cells to Enzalutamide},
journal = {Marine Drugs},
year = {2023},
volume = {21},
publisher = {Multidisciplinary Digital Publishing Institute (MDPI)},
month = {jan},
url = {https://doi.org/10.3390%2Fmd21010054},
number = {1},
pages = {54},
doi = {10.3390/md21010054}
}
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Dyshlovoy, Sergey A., et al. “New Marine Fungal Deoxy-14,15-Dehydroisoaustamide Resensitizes Prostate Cancer Cells to Enzalutamide.” Marine Drugs, vol. 21, no. 1, Jan. 2023, p. 54. https://doi.org/10.3390%2Fmd21010054.