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.
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