title: Inhibition of the PI3K/AKT-NF-κB pathway with curcumin enhanced radiation-induced apoptosis in human Burkitt's lymphoma.
abstract: 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.
authors.affiliation: Department of Radiotherapy, the First Hospital of China Medical University, China.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Qiao
authors.forename: Yuanjun
authors.initials: Y
authors.lastname: Jiang
authors.forename: Guang
authors.initials: G
authors.lastname: Li
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects*; D002051:Burkitt Lymphoma / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D002867:Chromones / Q000494:pharmacology; D003474:Curcumin / Q000494:pharmacology*; D006801:Humans; D007295:Inositol Phosphates / Q000494:pharmacology; D009025:Morpholines / Q000494:pharmacology; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000502:physiology; D058539:Phosphatidylinositol 3-Kinase / Q000502:physiology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000502:physiology; D011839:Radiation, Ionizing; D015398:Signal Transduction / Q000187:drug effects* / Q000528:radiation effects*
chemical_list: C435044:1-((1-O-octadecyl-2-O-methylglycero)phospho)-3-deoxy-myo-inositol; D000972:Antineoplastic Agents, Phytogenic; D002867:Chromones; D007295:Inositol Phosphates; D009025:Morpholines; D016328:NF-kappa B; D000081082:Phosphoinositide-3 Kinase Inhibitors; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D003474:Curcumin