Several studies suggested that curcumin inhibits growth of malignant cells via inhibition of cyclooxygenase-2 (COX-2) activity. Other studies indicated that epidermal growth factor receptor (EGFR) is ...also inhibited by curcumin in vitro and in vivo. Moreover, recent investigations revealed an intracellular cross-talk between EGFR signaling and the COX-2 pathway. Our aim was to evaluate whether the curcumin inhibitory effect on the survival of cancer cells is associated with simultaneous down-regulation of COX-2 and EGFR and inhibition of Erk1/2 (extra-cellular signal regulated kinase) signaling pathway.
Lung and pancreas adenocarcinoma cell lines co-expressing COX-2 and EGFR (PC-14 and p34, respectively) and those expressing EGFR but deficient in COX-2 (H1299 and Panc-1, respectively) were exposed for 72 h to curcumin (0-50 microM). Cell viability was assessed by the XTT assay. Apoptosis was determined by FACS analysis. COX-2, EGFR, ErbB-2 and p-Erk1/2 expressions were measured by Western blot analysis.
Curcumin's inhibitory effect on survival and apoptosis of lung and pancreatic adenocarcinoma cell lines was significantly higher in the COX-2-expressing cells than in the COX-2-deficient cells. In the p34 and PC-14 cells, curcumin decreased COX-2, EGFR and p-Erk1/2 expressions in a dose-dependent manner. However, in the Panc-1 and H1299 cell lines, which did not express COX-2, curcumin did not affect EGFR levels.
Curcumin co-inhibited COX-2 and EGFR expression and decreased Erk1/2 activity. This inhibition was associated with decreased survival and enhanced induction of apoptosis in lung and pancreatic adenocarcinoma cells.
Objectives/Hypothesis:
To investigate whether curcumin enhances the cytotoxic effect of radiotherapy in head and neck squamous cell carcinoma (HNSCC).
Methods:
HNSCC cell lines SCC‐1, SCC‐9, KB, as ...well as A431 cell line were treated with curcumin, irradiation, or their combination. Cell viability was evaluated by XTT assay. Cyclooxygenase‐2 (COX‐2), epithelial growth factor receptor (EGFR), and p‐Erk1/2 were measured by Western blot analysis. CD‐1 athymic nude mice with orthotopic implanted SCC‐1 cells, were treated with control diet, curcumin containing diet, local single‐dose radiation, or combination.
Results:
Curcumin (IC50 range, 15–22 μM) and radiation inhibited cell viability in all cell lines were tested. The combination of curcumin and radiation resulted in additive effect. Curcumin decreased COX‐2 expression and inhibited phosphorylation of EGFR in SCC‐1 cells. In tumor‐bearing mice the combination regimen showed a decrease in both tumor weight (25%, P = .09) and tumor size (15%, P = .23) compared to the nontreated mice.
Conclusions:
Curcumin inhibited HNSCC cell growth and augmented the effect of radiation in vitro and in vivo. A possible mechanism is inhibition of COX‐2 expression and EGFR phosphorylation. Laryngoscope, 2009
