Inhibition of the PI3K/AKT-NF-κB pathway with curcumin enhanced radiation-induced apoptosis in Human Burkitt's Lymphoma

The phosphatidylinositol-3-kinase (pi3k) / protein kinase b (akt) signal transduction pathway is commonly misregulated in lymphoma and associated with tumorigenesis and enhanced resistance to radiotherapy. curcumin has been shown to inhibit the pi3k/akt signal transduction pathway in several tumor models. in this study,we found that curcumin inhibits constitutive and radiation-induced expression of the pi3k/akt pathway and its downstream regulator nuclear factor kappab (nf-κb) in human burkitt's lymphoma,a high-grade non- hodgkin's lymphoma (nhl). we further demonstrated that the blockage of radiation-induced activation of the pi3k/akt pathway and its downstream regulator nf-κb by either curcumin or specific pi3/akt inhibitors (ly294002 for pi3k or sh-5 for akt) enhance apoptosis in three human burkitt's lymphoma cell lines (namalwa,ramos,and raji) that were treated with ionizing radiation. however,no synergic effect on radiation-induced apoptosis was found in the cells co-pretreated with curcumin combined with ly294002 or curcumin combined with sh-5. the results from this study suggest that curcumin might play an important role in radiotherapy of high-grade nhl through inhibition of the pi3k/akt-dependent nf-κb pathway. © the japanese pharmacological society.