New Guanidine Alkaloids Batzelladines O and P from the Marine Sponge Monanchora pulchra Induce Apoptosis and Autophagy in Prostate Cancer Cells
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New Guanidine Alkaloids Batzelladines O and P from the Marine Sponge Monanchora pulchra Induce Apoptosis and Autophagy in Prostate Cancer Cells. / Dyshlovoy, Sergey A.; Shubina, Larisa K.; Makarieva, Tatyana N.; Guzii, Alla G.; Hauschild, Jessica; Strewinsky, Nadja; Berdyshev, Dmitrii V.; Kudryashova, Ekaterina K.; Menshov, Alexander S.; Popov, Roman S.; Dmitrenok, Pavel S.; Graefen, Markus; Bokemeyer, Carsten; Amsberg, Gunhild von.
In: MAR DRUGS, Vol. 20, No. 12, 738, 25.11.2022.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - New Guanidine Alkaloids Batzelladines O and P from the Marine Sponge Monanchora pulchra Induce Apoptosis and Autophagy in Prostate Cancer Cells
AU - Dyshlovoy, Sergey A.
AU - Shubina, Larisa K.
AU - Makarieva, Tatyana N.
AU - Guzii, Alla G.
AU - Hauschild, Jessica
AU - Strewinsky, Nadja
AU - Berdyshev, Dmitrii V.
AU - Kudryashova, Ekaterina K.
AU - Menshov, Alexander S.
AU - Popov, Roman S.
AU - Dmitrenok, Pavel S.
AU - Graefen, Markus
AU - Bokemeyer, Carsten
AU - Amsberg, Gunhild von
PY - 2022/11/25
Y1 - 2022/11/25
N2 - Two new guanidine alkaloids, batzelladines O (1) and P (2), were isolated from the deep-water marine sponge Monanchora pulchra. The structures of these metabolites were determined by NMR spectroscopy, mass spectrometry, and ECD. The isolated compounds exhibited cytotoxic activity in human prostate cancer cells PC3, PC3-DR, and 22Rv1 at low micromolar concentrations and inhibited colony formation and survival of the cancer cells. Batzelladines O (1) and P (2) induced apoptosis, which was detected by Western blotting as caspase-3 and PARP cleavage. Additionally, induction of pro-survival autophagy indicated as upregulation of LC3B-II and suppression of mTOR was observed in the treated cells. In line with this, the combination with autophagy inhibitor 3-methyladenine synergistically increased the cytotoxic activity of batzelladines O (1) and P (2). Both compounds were equally active in docetaxel-sensitive and docetaxel-resistant prostate cancer cells, despite exhibiting a slight p-glycoprotein substrate-like activity. In combination with docetaxel, an additive effect was observed. In conclusion, the isolated new guanidine alkaloids are promising drug candidates for the treatment of taxane-resistant prostate cancer.
AB - Two new guanidine alkaloids, batzelladines O (1) and P (2), were isolated from the deep-water marine sponge Monanchora pulchra. The structures of these metabolites were determined by NMR spectroscopy, mass spectrometry, and ECD. The isolated compounds exhibited cytotoxic activity in human prostate cancer cells PC3, PC3-DR, and 22Rv1 at low micromolar concentrations and inhibited colony formation and survival of the cancer cells. Batzelladines O (1) and P (2) induced apoptosis, which was detected by Western blotting as caspase-3 and PARP cleavage. Additionally, induction of pro-survival autophagy indicated as upregulation of LC3B-II and suppression of mTOR was observed in the treated cells. In line with this, the combination with autophagy inhibitor 3-methyladenine synergistically increased the cytotoxic activity of batzelladines O (1) and P (2). Both compounds were equally active in docetaxel-sensitive and docetaxel-resistant prostate cancer cells, despite exhibiting a slight p-glycoprotein substrate-like activity. In combination with docetaxel, an additive effect was observed. In conclusion, the isolated new guanidine alkaloids are promising drug candidates for the treatment of taxane-resistant prostate cancer.
KW - Animals
KW - Male
KW - Humans
KW - Guanidine/pharmacology
KW - Docetaxel/pharmacology
KW - Guanidines/pharmacology
KW - Porifera/chemistry
KW - Apoptosis
KW - Cell Line, Tumor
KW - Antineoplastic Agents/pharmacology
KW - Prostatic Neoplasms/drug therapy
KW - Autophagy
KW - Alkaloids/pharmacology
U2 - 10.3390/md20120738
DO - 10.3390/md20120738
M3 - SCORING: Journal article
C2 - 36547885
VL - 20
JO - MAR DRUGS
JF - MAR DRUGS
SN - 1660-3397
IS - 12
M1 - 738
ER -