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000296197 1001_ $$0P:(DE-He78)3caae9893e3b2704f7bb5a9646ef084d$$aJennemann, Richard$$b0$$eFirst author$$udkfz
000296197 245__ $$aGlucosylceramide Synthase Inhibition in Combination with Aripiprazole Sensitizes Hepatocellular Cancer Cells to Sorafenib and Doxorubicin.
000296197 260__ $$aBasel$$bMolecular Diversity Preservation International$$c2025
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000296197 520__ $$aHepatocellular carcinoma (HCC) is one of the leading causes of cancer deaths due to its late diagnosis and restricted therapeutic options. Therefore, the search for appropriate alternatives to commonly applied therapies remains an area of high clinical need. Here we investigated the therapeutic potential of the glucosylceramide synthase (GCS) inhibitor Genz-123346 and the cationic amphiphilic drug aripiprazole on the inhibition of Huh7 and Hepa 1-6 hepatocellular cancer cell and tumor microsphere growth. Single and combinatorial treatments with both drugs at 5 µM concentration led to efficient cell cycle arrest, reduced expression of cyclins A and E, increased lipid storage in lysosomal compartments, accompanied by increased uptake of lysotracker, and elevated expression of the autophagy marker Lc3 II. Both drugs affected mitochondrial function, indicated by altered mitotracker uptake and impaired mitochondrial respiration. Aripiprazole in monotherapy, or even more pronounced in combination with Genz, also potentiated the effect of the cytostatic drugs sorafenib and doxorubicin on tumor cell- and tumor spheroid-growth inhibition. Targeting GCS with Genz with the parallel application of cationic amphiphilic drugs such as aripiprazole in combination with cytostatic drugs may thus represent a potent therapeutic approach in the treatment of HCC and potentially other cancer types.
000296197 536__ $$0G:(DE-HGF)POF4-311$$a311 - Zellbiologie und Tumorbiologie (POF4-311)$$cPOF4-311$$fPOF IV$$x0
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000296197 650_7 $$2Other$$aGenz
000296197 650_7 $$2Other$$aanti-psychotic drugs
000296197 650_7 $$2Other$$aaripiprazole
000296197 650_7 $$2Other$$acationic amphiphilic drugs (CAD)
000296197 650_7 $$2Other$$adoxorubicin
000296197 650_7 $$2Other$$aglucosylceramide synthase
000296197 650_7 $$2Other$$ahepatocellular tumor spheroids
000296197 650_7 $$2Other$$alysosomal function
000296197 650_7 $$2Other$$amitochondrial function
000296197 650_7 $$2Other$$asorafenib
000296197 650_7 $$09ZOQ3TZI87$$2NLM Chemicals$$aSorafenib
000296197 650_7 $$0EC 2.4.1.-$$2NLM Chemicals$$aGlucosyltransferases
000296197 650_7 $$080168379AG$$2NLM Chemicals$$aDoxorubicin
000296197 650_7 $$082VFR53I78$$2NLM Chemicals$$aAripiprazole
000296197 650_7 $$0EC 2.4.1.80$$2NLM Chemicals$$aceramide glucosyltransferase
000296197 650_7 $$2NLM Chemicals$$aAntineoplastic Agents
000296197 650_2 $$2MeSH$$aHumans
000296197 650_2 $$2MeSH$$aCarcinoma, Hepatocellular: drug therapy
000296197 650_2 $$2MeSH$$aCarcinoma, Hepatocellular: pathology
000296197 650_2 $$2MeSH$$aCarcinoma, Hepatocellular: metabolism
000296197 650_2 $$2MeSH$$aSorafenib: pharmacology
000296197 650_2 $$2MeSH$$aLiver Neoplasms: drug therapy
000296197 650_2 $$2MeSH$$aLiver Neoplasms: pathology
000296197 650_2 $$2MeSH$$aLiver Neoplasms: metabolism
000296197 650_2 $$2MeSH$$aGlucosyltransferases: antagonists & inhibitors
000296197 650_2 $$2MeSH$$aGlucosyltransferases: metabolism
000296197 650_2 $$2MeSH$$aDoxorubicin: pharmacology
000296197 650_2 $$2MeSH$$aAripiprazole: pharmacology
000296197 650_2 $$2MeSH$$aCell Line, Tumor
000296197 650_2 $$2MeSH$$aDrug Synergism
000296197 650_2 $$2MeSH$$aCell Proliferation: drug effects
000296197 650_2 $$2MeSH$$aMitochondria: drug effects
000296197 650_2 $$2MeSH$$aMitochondria: metabolism
000296197 650_2 $$2MeSH$$aAntineoplastic Agents: pharmacology
000296197 7001_ $$0P:(DE-He78)a0a16a2508287abe75725c2a00627ca2$$aVolz, Martina$$b1$$udkfz
000296197 7001_ $$0P:(DE-HGF)0$$aFrias-Soler, Roberto Carlos$$b2
000296197 7001_ $$0P:(DE-He78)94ae391f53fb9285e1b68f9930615af1$$aSchulze, Almut$$b3$$udkfz
000296197 7001_ $$0P:(DE-He78)027fe772631b4a2d7a45c439cdd75ff2$$aRichter, Karsten$$b4$$udkfz
000296197 7001_ $$0P:(DE-He78)6093fbefe5b51f07e37146565925d681$$aKaden, Sylvia$$b5$$udkfz
000296197 7001_ $$0P:(DE-He78)a928ded2085c8911822370cad0b4a728$$aSandhoff, Roger$$b6$$eLast author$$udkfz
000296197 773__ $$0PERI:(DE-600)2019364-6$$a10.3390/ijms26010304$$gVol. 26, no. 1, p. 304 -$$n1$$p304$$tInternational journal of molecular sciences$$v26$$x1422-0067$$y2025
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