title: Curcumin enhances the response of non-Hodgkin's lymphoma cells to ionizing             radiation through further induction of cell cycle arrest at the G2/M phase and             inhibition of mTOR phosphorylation.
abstract: It is crucial to enhance tumor radiosensitivity for the purpose of both lowering the dose of ionizing radiation (IR) and achieving higher antitumor efficacy. We identified curcumin as a radiosensitizer to enhance non-Hodgkin's lymphoma (NHL) cell response to IR in vitro and further investigated the mechanism mediating this effect. We treated Namalwa, Ramos and Raji cell lines with vehicle, curcumin, IR and curcumin-IR. Cell viability and cell cycle distribution were determined to ascertain the radiosensitization effect of curcumin. DNA damage-related proteins, cell cycle regulatory proteins, phosphorylation of mammalian target of rapamycin (mTOR) and the nuclear translocation of the downstream nuclear factor-κB (NF-κB) target were examined by western blotting. Treatment with curcumin led to decreased viability of all three types of NHL cells and had a profound radiosensitization effect. Pre-treatment with curcumin at a low concentration of 2 µmol/l increased IR-induced G2/M arrest in the cell cycle and increased the expression of cyclin-dependent kinase inhibitors, p21cip1 and p53. However, this effect was blocked when NHL cells were pre-treated with 10 µmol/l of KU55933, a specific inhibitor of ataxia-telangiectasia-mutated (ATM). Pre-treatment with curcumin inhibited the phosphorylation of mTOR and the nuclear translocation of the downstream NF-κB target induced by IR. Curcumin enhanced the cell response to IR in NHL mediated through the induction of G2/M phase arrest and the inhibition of both a constitutive and IR-induced activation of the mTOR-NF-κB pathway. This offers great potential for curcumin to be used in conjunction with radiotherapy for NHL in order to increase the efficiency of the treatment.
authors.affiliation: Department of Radiotherapy, The First Hospital of China Medical University, Shenyang 110001, PR 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: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D015153:Blotting, Western; D059447:Cell Cycle Checkpoints / Q000187:drug effects* / Q000528:radiation effects; D002455:Cell Division / Q000187:drug effects* / Q000528:radiation effects; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D003474:Curcumin / Q000494:pharmacology*; D016195:G2 Phase / Q000187:drug effects* / Q000528:radiation effects; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D011836:Radiation Tolerance / Q000187:drug effects* / Q000528:radiation effects; D011839:Radiation, Ionizing; D015398:Signal Transduction; D013347:Subcellular Fractions; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D016328:NF-kappa B; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D003474:Curcumin