2. Academic Validation
  3. New Guanidine Alkaloids Batzelladines O and P from the Marine Sponge Monanchora pulchra Induce Apoptosis and Autophagy in Prostate Cancer Cells

New Guanidine Alkaloids Batzelladines O and P from the Marine Sponge Monanchora pulchra Induce Apoptosis and Autophagy in Prostate Cancer Cells

  • Mar Drugs. 2022 Nov 25;20(12):738. doi: 10.3390/md20120738.
Sergey A Dyshlovoy 1 2 3,  Larisa K Shubina 4,  Tatyana N Makarieva 4,  Alla G Guzii 4,  Jessica Hauschild 1 2,  Nadja Strewinsky 1,  Dmitrii V Berdyshev 4,  Ekaterina K Kudryashova 4,  Alexander S Menshov 4,  Roman S Popov 4,  Pavel S Dmitrenok 4,  Markus Graefen 2,  Carsten Bokemeyer 1,  Gunhild von Amsberg 1 2
Affiliations

Affiliations

  • 1 Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald-Tumorzentrum-University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany.
  • 2 Martini-Klinik, Prostate Cancer Center, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany.
  • 3 Institute of High Technologies and Advanced Materials, Far Eastern Federal University, 690922 Vladivostok, Russia.
  • 4 G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of the Russian Academy of Sciences, Pr. 100-let Vladivostoku 159, 690022 Vladivostok, Russia.
PMID: 36547885 DOI: 10.3390/md20120738
Abstract

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.

Keywords

Monanchora pulchra; anticancer activity; apoptosis; autophagy; batzelladines; p-glycoprotein; prostate cancer; sponge.

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