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The Curcumin Analog C-150, Influencing NF-κB, UPR and Akt/Notch Pathways Has Potent Anticancer Activity In Vitro and In Vivo
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The Curcumin Analog C-150, Influencing NF-κB, UPR and Akt/Notch Pathways Has Potent Anticancer Activity In Vitro and In Vivo
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Journal Article
The Curcumin Analog C-150, Influencing NF-κB, UPR and Akt/Notch Pathways Has Potent Anticancer Activity In Vitro and In Vivo
2016
Overview
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.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
/ Animals
/ Antineoplastic Agents - chemistry
/ Brain Neoplasms - drug therapy
/ Brain Neoplasms - metabolism
/ Curcumin
/ Curcumin - analogs & derivatives
/ Drug Screening Assays, Antitumor
/ Female
/ Gene Expression Regulation, Neoplastic
/ Glioma
/ Humans
/ Kinases
/ Medicine and Health Sciences
/ Mice
/ NF-kappa B - antagonists & inhibitors
/ Proteins
/ Proto-Oncogene Proteins c-akt - antagonists & inhibitors
/ Rats
/ Receptors, Notch - antagonists & inhibitors
/ Receptors, Notch - metabolism
/ Research and Analysis Methods
/ Tumors
