Curcumin improves the antitumor effect of X-ray irradiation by blocking the NF-κB pathway

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.

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

“…These results suggest that the phosphorylation of ATM plays a crucial role in G2/M phase arrest induced by IR and curcumin through the regulation of p53 and p21 cip1 expression. We previously demonstrated that curcumin sensitizes NHL cells to IR-induced apoptosis through decreasing the NF-κB expression and by inhibiting its nuclear localization induced by IR exposure (13). However, the details of the mechanism by which curcumin regulates IR-induced activation of NF-κB remains unclear.…”

“…Cell viability was determined with the tetrazolium salt water-soluble tetrazolium salt assay (Roche Diagnostics GmbH, Penzberg, Germany) as previously described (13). The results were expressed as a percentage of cell viability for each concentration of curcumin with respect to the controls.…”

“…Namalwa, Ramos and Raji cells were incubated with various stimuli for the indicated times, and the total and nuclear extracts were obtained as previously described (13). The protein content was measured by the Bradford method (Bio-Rad, Hercules, CA, USA).…”

“…Curcumin has exhibited varying effects on radiation sensitivity in different cancer cell types and its effect as a radiosensitizer has been supported in a variety of tumors including prostate, colorectal and ovarian cancers (8)(9)(10)(11)(12). Likewise, we previously demonstrated that curcumin may enhance IR-induced apoptosis in NHL (13).…”

Spices for Prevention and Treatment of Cancers

“…The apoptosis induced by curcumin was through an amplification of endoplasmic reticulum (ER) stress, which possibly resulted from the accumulation of misfolded nuclear receptor corepressor protein in the ER [83]. In another study, in Burkitt’s lymphoma cell lines, ionizing radiation-induced apoptosis and G 2 /M phase arrest were increased by pretreatment of curcumin through NF-κB pathway [84]. Additionally, in HuT-78 cells (T-cell lymphoma), curcumin-mediated rapid generation of ROS induced apoptosis through modulating different cell survival and cell death pathways [85].…”