000864928 001__ 864928
000864928 005__ 20210130002759.0
000864928 0247_ $$2doi$$a10.1016/j.bmc.2019.115044
000864928 0247_ $$2ISSN$$a0968-0896
000864928 0247_ $$2ISSN$$a1464-3391
000864928 0247_ $$2pmid$$apmid:31443950
000864928 0247_ $$2WOS$$aWOS:000484396400012
000864928 037__ $$aFZJ-2019-04531
000864928 082__ $$a610
000864928 1001_ $$0P:(DE-HGF)0$$aWang, Chenyin$$b0
000864928 245__ $$aThe tetrahydroxanthone-dimer phomoxanthone A is a strong inducer of apoptosis in cisplatin-resistant solid cancer cells
000864928 260__ $$aAmsterdam [u.a.]$$bElsevier$$c2019
000864928 3367_ $$2DRIVER$$aarticle
000864928 3367_ $$2DataCite$$aOutput Types/Journal article
000864928 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1568265078_2892
000864928 3367_ $$2BibTeX$$aARTICLE
000864928 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000864928 3367_ $$00$$2EndNote$$aJournal Article
000864928 520__ $$aPlatinum compounds are the first-line therapy for many types of cancer. However, drug resistance has frequently been reported for and is a major limitation of platinum-based chemotherapy in the clinic. In the current study, we examined the anti-tumor activity of phomoxanthone A (PXA), a tetrahydroxanthone dimer isolated from the endophytic fungus Phomopsis longicolla, in several solid cancer cell lines and their cisplatin-resistant sub-cell lines. PXA showed strong cytotoxic effects with IC50 values in the high nanomolar or low micromolar range in MTT assays. IC50 values of PXA were lower than those of cisplatin. Remarkably, equipotent anti-cancer activity was found in cisplatin-sensitive and respective cisplatin-resistant cells. Anticancer effects of PXA were studied in further detail in ovarian cancer (A2780) and bladder cancer (J82) cell pairs. PXA led to rapid depolarization of the mitochondrial membrane potential and strong activation of caspase 3 and 7, eventually resulting in strong induction of apoptosis. These effects occurred again both in sensitive and resistant cell lines. IC50 values of PXA from MTT and mitochondrial membrane depolarization assays were in good agreement. Configurational free energy computations indicate that both the neutral and singly negatively charged PXA show membrane partitioning and can penetrate the inner mitochondrial membrane. PXA treatment did not damage the plasma membranes of cancer cells, thus excluding unspecific membrane effects. Further, PXA had neither an effect on intracellular ROS nor on reduction of ROS after hydrogen peroxide treatment. In conclusion, our studies present PXA as a natural compound with strong apoptotic anticancer effects against platinum-resistant solid cancers. This may open new treatment options in clinically resistant malignancies.
000864928 536__ $$0G:(DE-HGF)POF3-511$$a511 - Computational Science and Mathematical Methods (POF3-511)$$cPOF3-511$$fPOF III$$x0
000864928 536__ $$0G:(DE-Juel1)hkf7_20170501$$aForschergruppe Gohlke (hkf7_20170501)$$chkf7_20170501$$fForschergruppe Gohlke$$x1
000864928 588__ $$aDataset connected to CrossRef
000864928 7001_ $$0P:(DE-HGF)0$$aEngelke, Laura$$b1
000864928 7001_ $$0P:(DE-HGF)0$$aBickel, David$$b2
000864928 7001_ $$0P:(DE-HGF)0$$aHamacher, Alexandra$$b3
000864928 7001_ $$0P:(DE-HGF)0$$aFrank, Marian$$b4
000864928 7001_ $$0P:(DE-HGF)0$$aProksch, Peter$$b5
000864928 7001_ $$0P:(DE-Juel1)172663$$aGohlke, Holger$$b6$$ufzj
000864928 7001_ $$0P:(DE-HGF)0$$aKassack, Matthias U.$$b7$$eCorresponding author
000864928 773__ $$0PERI:(DE-600)1501507-5$$a10.1016/j.bmc.2019.115044$$gp. 115044 -$$n19$$p115044$$tBioorganic & medicinal chemistry$$v27$$x0968-0896$$y2019
000864928 909CO $$ooai:juser.fz-juelich.de:864928$$pVDB
000864928 9101_ $$0I:(DE-588b)5008462-8$$6P:(DE-Juel1)172663$$aForschungszentrum Jülich$$b6$$kFZJ
000864928 9131_ $$0G:(DE-HGF)POF3-511$$1G:(DE-HGF)POF3-510$$2G:(DE-HGF)POF3-500$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bKey Technologies$$lSupercomputing & Big Data$$vComputational Science and Mathematical Methods$$x0
000864928 9141_ $$y2019
000864928 915__ $$0StatID:(DE-HGF)0420$$2StatID$$aNationallizenz
000864928 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS
000864928 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline
000864928 915__ $$0StatID:(DE-HGF)0310$$2StatID$$aDBCoverage$$bNCBI Molecular Biology Database
000864928 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bBIOORGAN MED CHEM : 2017
000864928 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search
000864928 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC
000864928 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List
000864928 915__ $$0StatID:(DE-HGF)0110$$2StatID$$aWoS$$bScience Citation Index
000864928 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection
000864928 915__ $$0StatID:(DE-HGF)0111$$2StatID$$aWoS$$bScience Citation Index Expanded
000864928 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences
000864928 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews
000864928 915__ $$0StatID:(DE-HGF)9900$$2StatID$$aIF < 5
000864928 920__ $$lyes
000864928 9201_ $$0I:(DE-Juel1)JSC-20090406$$kJSC$$lJülich Supercomputing Center$$x0
000864928 9201_ $$0I:(DE-Juel1)NIC-20090406$$kNIC$$lJohn von Neumann - Institut für Computing$$x1
000864928 9201_ $$0I:(DE-Juel1)ICS-6-20110106$$kICS-6$$lStrukturbiochemie$$x2
000864928 980__ $$ajournal
000864928 980__ $$aVDB
000864928 980__ $$aI:(DE-Juel1)JSC-20090406
000864928 980__ $$aI:(DE-Juel1)NIC-20090406
000864928 980__ $$aI:(DE-Juel1)ICS-6-20110106
000864928 980__ $$aUNRESTRICTED
000864928 981__ $$aI:(DE-Juel1)IBI-7-20200312