title: The Curcumin Analog C-150, Influencing NF-κB, UPR and Akt/Notch Pathways Has Potent Anticancer Activity In Vitro and In Vivo.
abstract: C-150 a Mannich-type curcumin derivative, exhibited pronounced cytotoxic effects against eight glioma cell lines at micromolar concentrations. Inhibition of cell proliferation by C-150 was mediated by affecting multiple targets as confirmed at transcription and protein level. C-150 effectively reduced the transcription activation of NFkB, inhibited PKC-alpha which are constitutively over-expressed in glioblastoma. The effects of C-150 on the Akt/ Notch signaling were also demonstrated in a Drosophila tumorigenesis model. C-150 reduced the number of tumors in Drosophila with similar efficacy to mitoxantrone. In an in vivo orthotopic glioma model, C-150 significantly increased the median survival of treated nude rats compared to control animals. The multi-target action of C-150, and its preliminary in vivo efficacy would render this curcumin analogue as a potent clinical candidate against glioblastoma.
authors.affiliation: AVIDIN Ltd., Szeged, Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Hackler
authors.affiliation: AVIDIN Ltd., Szeged, Hungary.
authors.forename: Béla
authors.initials: B
authors.lastname: Ózsvári
authors.affiliation: AVIDIN Ltd., Szeged, Hungary.
authors.forename: Márió
authors.initials: M
authors.lastname: Gyuris
authors.affiliation: Department of Pharmaceutical Technology, University of Szeged, Szeged, Hungary.
authors.forename: Péter
authors.initials: P
authors.lastname: Sipos
authors.affiliation: AVICOR Ltd., Szeged, Hungary.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Fábián
authors.affiliation: AVICOR Ltd., Szeged, Hungary.
authors.forename: Eszter
authors.initials: E
authors.lastname: Molnár
authors.affiliation: Institute of Biochemistry, Biological Research Center of the Hungarian Academy of Sciences, Szeged, Hungary.
authors.forename: Annamária
authors.initials: A
authors.lastname: Marton
authors.affiliation: AVIDIN Ltd., Szeged, Hungary.|Institute of Genetics, Biological Research Center of the Hungarian Academy of Sciences, Szeged, Hungary.
authors.forename: Nóra
authors.initials: N
authors.lastname: Faragó
authors.affiliation: Institute of Genetics, Biological Research Center of the Hungarian Academy of Sciences, Szeged, Hungary.
authors.forename: József
authors.initials: J
authors.lastname: Mihály
authors.affiliation: AVIDIN Ltd., Szeged, Hungary.
authors.forename: Lajos István
authors.initials: LI
authors.lastname: Nagy
authors.affiliation: Institute of Genetics, Biological Research Center of the Hungarian Academy of Sciences, Szeged, Hungary.
authors.forename: Tibor
authors.initials: T
authors.lastname: Szénási
authors.affiliation: AVIDIN Ltd., Szeged, Hungary.
authors.forename: Andrea
authors.initials: A
authors.lastname: Diron
authors.affiliation: Institute of Biophysics, Biological Research Center of the Hungarian Academy of Sciences, Szeged, Hungary.
authors.forename: Árpád
authors.initials: Á
authors.lastname: Párducz
authors.affiliation: AVIDIN Ltd., Szeged, Hungary.
authors.forename: Iván
authors.initials: I
authors.lastname: Kanizsai
authors.affiliation: AVIDIN Ltd., Szeged, Hungary.|Institute of Genetics, Biological Research Center of the Hungarian Academy of Sciences, Szeged, Hungary.
authors.forename: László G
authors.initials: LG
authors.lastname: Puskás
mesh_terms: D000178:Acrylamides / Q000737:chemistry*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003474:Curcumin / Q000031:analogs & derivatives* / Q000737:chemistry*; D004331:Drosophila melanogaster; D004354:Drug Screening Assays, Antitumor; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D008546:Melanoma, Experimental; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D009368:Neoplasm Transplantation; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors*; D051381:Rats; D011923:Rats, Nude; D051880:Receptors, Notch / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic; D056811:Unfolded Protein Response / Q000187:drug effects*
chemical_list: D000178:Acrylamides; D000970:Antineoplastic Agents; C000609464:C-150 curcumin; D016328:NF-kappa B; D051880:Receptors, Notch; D051057:Proto-Oncogene Proteins c-akt; D003474:Curcumin