Curcumin, a polyphenolic compound derived from turmeric which commonly found in Asian diet, has been well known of its potent anti-tumourigenic and anti-proliferative property at certain doses. Its apoptosis-inducing effect and targeting of NF-Kappa B pathway have been recently reported, however, the other molecular mechanism(s) of action of this drug remain to be elucidated. Telomerase, a reverse transcriptase that maintains telomere length, is highly activated in tumor cells and practically absent in somatic cells and hence considered a potential marker for tumorigenesis Telomerase, therefore, has been proposed to represent a novel and potentially selective target for cancer therapy. In our present study, we have investigated the anti-proliferative activity, DNA damage induction, telomere-telomerase regulation in human glioblastoma (A172, KNS60 and U251) and medulloblastoma cell line (ONS76) following different doses of curcumin. Normal human primary fibroblasts and BJ1-hTERT cell line were used as control cell types. Curcumin induced a dose-dependent effect (doses from 0 to 100 µM) on cell viability in the different brain tumour cell lines. Telomerase-positive cell lines used in the study exhibited higher sensitivity to curcumin compared to the normal human fibroblasts. Curcumin concentrations which induced LC50 for each cell line were selected for subsequent experiments. LC 50 concentrations were higher for normal cells (90 µM) compared to the telomerase positive cancer cell lines (30 to 50 µM). Most of the brain tumour cell lines showed higher percentage of cells in sub-G1 phase except the glioblastoma cell line (A172).The extent of DNA damage induced by curcumin was measured by single cell gel electrophoresis (comet) assay. Normal human fibroblasts displayed greater DNA damage compared to the cancer cell lines. Inhibition of telomerase activity was seen in all the telomerase-positive cell lines tested following treatment with curcumin. Long-term treatment with curcumin has also resulted in significant telomere shortening in cancer cell lines. Curcumin suppressed key signalling pathways which are elevated in cancer cell lines as analysed by gene expression analysis. Results from the present study suggest that telomerase status plays an important role in the induction of cell cycle arrest, anti-proliferative effect and apoptosis in human brain tumour cell lines by curcumin.
98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA