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.
Highlights
Malignant glioma is the most common cancer of the central nervous system in adults with a median survival time of nine months following surgery, radiotherapy and chemotherapy
The cytotoxicity of C-150 curcumin analogue was assessed in a panel of human glioblastoma cell lines using the MTS assay
The present study demonstrated a potent, cell death-inducing effect of C-150, an analogue of the natural compound, curcumin, in human glioma cells
Summary
Malignant glioma is the most common cancer of the central nervous system in adults with a median survival time of nine months following surgery, radiotherapy and chemotherapy. Despite advances in different therapies of glioblastoma, they are associated with significant side effects and only limited efficacy [1]. Many pieces of evidence point out the relevance of herbal medicines for cancer therapy and prevention, including polyunsaturated fatty acids [2,3,4], corosolic acid [5] and dietary phytochemicals among others [6,7,8]. Recent attention has focused on curcumin, known as diferuloyl methane, a polyphenolic, yellow pigment found in the rhizome of turmeric (Curcuma longa).
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