Marine alkaloid Monanchocidin a overcomes drug resistance by induction of autophagy and lysosomal membrane permeabilization
Dyshlovoy SA, Hauschild J, Amann KU, Tabakmakher KM, Venz S, Walther R, Guzii AG, Makarieva TN, Shubina LK, Fedorov SN, Stonik VA, Bokemeyer C, Balabanov S, Honecker F, Amsberg GV (2015)
Publication Type: Journal article
Publication year: 2015
Journal
Book Volume: 6
Pages Range: 17328-41
Journal Issue: 19
Abstract
Monanchocidin A (MonA) is a novel alkaloid recently isolated from the marine sponge Monanchora pulchra. The compound reveals cytotoxic activity in genitourinary cancers including cisplatin-sensitive and -resistant germ cell tumor (GCT) cell lines, hormone-sensitive and castration-resistant prostate carcinoma cell lines and different bladder carcinoma cell lines. In contrast, non-malignant cells were significantly less sensitive. MonA is highly synergistic with cisplatin in GCT cells. Induction of autophagy at lower and lysosomal membrane permeabilization (LMP) at higher concentrations were identified as the dominating modes of action. Cytotoxicity and protein degradation could be inhibited by 3-methyladenine, an inhibitor of autophagy. LMP was confirmed by loss of acridine orange staining of lysosoms and by release of cathepsin B. In conclusion, MonA exerts cytotoxic activity by mechanisms different from "classical" apoptosis, and could be a promising new compound to overcome resistance to standard therapies in genitourinary malignancies.
Authors with CRIS profile
Involved external institutions
Universitätsklinikum Hamburg-Eppendorf (UKE)
Germany (DE)
Russian Academy of Sciences / Росси́йская акаде́мия нау́к (RAS)
Russian Federation (RU)
Universität Greifswald
Germany (DE)
Germany (DE)
Russian Academy of Sciences / Росси́йская акаде́мия нау́к (RAS)
Russian Federation (RU)
Universität Greifswald
Germany (DE)
How to cite
APA:
Dyshlovoy, S.A., Hauschild, J., Amann, K.U., Tabakmakher, K.M., Venz, S., Walther, R.,... Amsberg, G.V. (2015). Marine alkaloid Monanchocidin a overcomes drug resistance by induction of autophagy and lysosomal membrane permeabilization. Oncotarget, 6(19), 17328-41. https://doi.org/10.18632/oncotarget.4175
MLA:
Dyshlovoy, Sergey A., et al. "Marine alkaloid Monanchocidin a overcomes drug resistance by induction of autophagy and lysosomal membrane permeabilization." Oncotarget 6.19 (2015): 17328-41.
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