| 1594 Differential Effects of p38 MAP Kinase Pathway Activation on the Survival of Osteoblasts, Endothelial Cells and Tumor Cells: Implications in Cancer Treatment | ||
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S. SUTTAMANATWONG, P. KUMAR, and P.J. POLVERINI, University of Minnesota, Minneapolis, USA Therapeutic g-irradiation is commonly used in cancer therapy. However, it has many adverse effects. This is particularly true for the treatment of oral and pharyngeal cancers where damage to bone often occurs. Recent studies indicate that activation of the p38 MAPK pathway may modulate angiogenesis and tumor growth by inducing endothelial cell and tumor cell apoptosis. In contrast, activation of p38 MAPK has been reported to enhance the survival of bone cells. Objective: To investigate if activation of p38 MAPK can enhance g-irradiation-induced endothelial and tumor cell death while protecting normal bone. Methods: Human dermal microvascular endothelial cells (HDMEC), human osteoblasts (NHOst), and an oral squamous carcinoma cell line (OSCC-3) were exposed to 7.5 Gy of g-irradiation in the presence or absence of sodium arsenite, an activator of the p38 MAPK pathway. After 72 hours, cell viability was determined using a modified MTT assay. Results: NHOst and HDMEC, when exposed to g-irradiation, showed significant cell death (18% and 30% respectively), whereas OSCC-3 cells were more resistant to g-irradiation (4%). Arsenite treatment alone increased the number of viable NHOst (41%) while inducing cell death in 21% and 51% of HDMEC and OSCC-3, respectively. Pretreatment of NHOst with arsenite completely protected NHOst from g-irradiation-induced cell death while increasing OSCC-3 cell death (18%). However, arsenite treatment did not enhance g-irradiation-induced endothelial cell death, which may be due to the additional effect of arsenite activation of the ERK1/2 and JNK pathways. As expected, pretreatment of HDMEC and OSCC-3 cells with ERK1/2 and JNK inhibitor further enhanced g-irradiation-induced cell death by 22% and 27% respectively. Conclusion: Our results suggests that activation of p38 MAPK may be a novel strategy to enhance g-irradiation-mediated cell death in tumor while protecting bone from the adverse effects of g-irradiation. This work was supported by NIH Grant DE 13161. | ||
| Seq #201 - Senior Category 11:00 AM-12:15 PM, Saturday, 15 March 2003 Henry B. Gonzalez Convention Center Exhibit Hall C | ||
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