New Marine Fungal Deoxy-14,15-Dehydroisoaustamide Resensitizes Prostate Cancer Cells to Enzalutamide
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New Marine Fungal Deoxy-14,15-Dehydroisoaustamide Resensitizes Prostate Cancer Cells to Enzalutamide. / Dyshlovoy, Sergey A.; Zhuravleva, Olesya I.; Hauschild, Jessica; Busenbender, Tobias; Pelageev, Dmitry N.; Yurchenko, Anton N.; Khudyakova, Yuliya V.; Antonov, Alexandr S.; Graefen, Markus; Bokemeyer, Carsten; von Amsberg, Gunhild.
In: MAR DRUGS, Vol. 21, No. 1, 54, 14.01.2023.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - New Marine Fungal Deoxy-14,15-Dehydroisoaustamide Resensitizes Prostate Cancer Cells to Enzalutamide
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 - 2023/1/14
Y1 - 2023/1/14
N2 - 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.
AB - 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.
KW - Humans
KW - Male
KW - Antineoplastic Agents/pharmacology
KW - Cell Line, Tumor
KW - Drug Resistance, Neoplasm
KW - Nitriles/pharmacology
KW - Phenylthiohydantoin/pharmacology
KW - Prostatic Neoplasms, Castration-Resistant/drug therapy
KW - Receptors, Androgen/metabolism
U2 - 10.3390/md21010054
DO - 10.3390/md21010054
M3 - SCORING: Journal article
C2 - 36662227
VL - 21
JO - MAR DRUGS
JF - MAR DRUGS
SN - 1660-3397
IS - 1
M1 - 54
ER -
