title: Curcumin improves the antitumor effect of X-ray irradiation by blocking the NF-κB pathway:  an in-vitro study of lymphoma.
abstract: Curcumin, a phenolic compound from the rhizomes of Curcuma longa, inhibits the growth of a variety of malignant cell types including lymphoma cells. We investigated the role of curcumin in modulating the response of Burkitt's lymphoma cells to ionizing radiation (IR) in vitro and explored the mechanisms that mediated this effect. We treated three Burkitt's lymphoma cell lines with vehicle, curcumin, IR, and curcumin in combination with IR. Cell viability, apoptosis, and cell cycle distribution were determined to ascertain the radiosensitization effect of curcumin. Nuclear factor-kappa B (NF-κB) activation was assessed by nuclear translocation of p65. Apoptosis-related proteins were monitored by western blot assay and real-time RT-PCR. Pretreatment of curcumin sensitized lymphoma cells to IR-induced apoptosis and increased G2/M phase arrest in the cell cycle distribution. Accordingly, the antiapoptotic Bcl-xL protein, cell cycle modulating protein CDC2, and cyclin B1 were downregulated by the curcumin treatment. IR activated NF-κB as evidenced by an increased nuclear p65 translocation and cytoplasmic IκBα expression. However, pretreatment with curcumin significantly decreased the nuclear translocation of p65 and cytoplasmic IκBα degradation. Survivin and hexokinase II, downstream effectors of NF-κB that mediate the antiapoptotic effect of NF-κB, were suppressed by the pretreatment of curcumin. These observations suggest that the activated NF-κB pathway plays a prosurvival role in Burkitt's lymphoma in response to IR. Curcumin blocks this pathway and has therapeutic potential for improving the antitumor effects of radiotherapy.
authors.affiliation: Departments of aRadiotherapy bUrology, The First Affiliated Hospital, China Medical University, Shenyang, 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: D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002051:Burkitt Lymphoma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects / Q000528:radiation effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects / Q000528:radiation effects; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D021381:Protein Transport / Q000187:drug effects / Q000528:radiation effects; D000077022:Survivin; D014965:X-Rays
chemical_list: C107489:BIRC5 protein, human; D020672:I-kappa B Proteins; D051034:Inhibitor of Apoptosis Proteins; D016328:NF-kappa B; D000077022:Survivin; D003474:Curcumin