PLoS One. 2016 Mar 4;11(3):e0149832. doi: 10.1371/journal.pone.0149832.

The Curcumin Analog C-150, Influencing NF-κB, UPR and Akt/Notch Pathways Has Potent Anticancer Activity In Vitro and In Vivo.

Hackler L Jr1, Ózsvári B1, Gyuris M1, Sipos P2, Fábián G3, Molnár E3, Marton A4, Faragó N1,5, Mihály J5, Nagy LI1, Szénási T5, Diron A1, Párducz Á6, Kanizsai I1, Puskás LG1,5.

 

Author information:

1AVIDIN Ltd., Szeged, Hungary.

2Department of Pharmaceutical Technology, University of Szeged, Szeged, Hungary.

3AVICOR Ltd., Szeged, Hungary.

4Institute of Biochemistry, Biological Research Center of the Hungarian Academy of Sciences, Szeged, Hungary.

5Institute of Genetics, Biological Research Center of the Hungarian Academy of Sciences, Szeged, Hungary.

6Institute of Biophysics, Biological Research Center of the Hungarian Academy of Sciences, Szeged, Hungary.

 

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.