ABSTRACT
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 microM) 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.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Carcinoma, Squamous Cell/radiotherapy , Curcumin/pharmacology , Head and Neck Neoplasms/radiotherapy , Animals , Cell Line, Tumor , Cell Survival/drug effects , Cyclooxygenase 2/metabolism , Dose-Response Relationship, Drug , ErbB Receptors/metabolism , Flow Cytometry , Mice , Mice, Nude , Mitogen-Activated Protein Kinase 1/antagonists & inhibitors , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3/antagonists & inhibitors , Mitogen-Activated Protein Kinase 3/metabolism , Phosphorylation/drug effectsABSTRACT
PURPOSE: To correlate p53 and ErbB receptors status with disease-free survival (DFS) and overall survival (OS) in locally advanced breast cancer. PATIENTS AND METHODS: Sixty patients were included in a single-center, open-label, phase II trial (1998-2003). Analysis of Erb receptors and p53 status and estrogen receptor/progesterone receptor data were available for 33 patients. Neoadjuvant epirubicin 75 mg/m2 and paclitaxel 175-200 mg/m2 were administered every 21 days. The patients underwent surgery and radiation therapy and adjuvant chemo/hormonotherapy. RESULTS: Approximately two thirds of the patients demonstrated overexpression of ErbB receptors and had mutant p53 overexpression. The disease recurred in 11/33 patients and 7 died (median follow-up 56 months). Detrimental effects on OS were established in cases of combined defective p53 expression and ErbB1-ErbB3 heterodimeric receptor overexpression. In contrast, normal p53 together with the same overexpressed heterodimeric combination of ErbB receptors showed no statistically significant effect. CONCLUSION: In terms of the clinical impact of combinations of ErbB receptors with or without mutant p53, only the overexpressed various ErbB1-ErbB3 dimeric combinations and the ErbB1/ErbB2/ErbB3 triplet combination with mutated p53 were related to a significantly poorer outcome. This observation may help in the development of new strategies required for blocking these molecular pathways and improving the outcome of patients with locally advanced breast cancer.
