Curcumin induces and enhances the PARP1-mediated parthanatos in diffuse large B cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma in adults. Although the development and application of novel therapeutic agents have improved patient survival, primary drug resistance and the management of relapsed/refractory disease remain major challenges. Curcumin, a natural polyphenol, exhibits broad-spectrum antitumor activity. However, its anti-DLBCL efficacy and underlying mechanisms have not been well characterized. The present study investigated whether curcumin inhibited DLBCL by inducing parthanatos, a form of programmed cell death. Results showed that curcumin exerted a concentration-dependent, caspase-independent cytotoxic effect on DLBCL cells, accompanied by an increase in DAPI-positive/propidium iodide-positive cells. Western blotting analysis revealed that curcumin upregulated poly(ADP-ribose) and poly(ADP-ribose) polymerase 1 (PARP-1) expression in whole-cell lysates. Moreover, nuclear expression levels of apoptosis-inducing factor (AIF) and macrophage migration inhibitory factor were significantly elevated compared with their cytoplasmic levels. Immunofluorescence staining further confirmed the increased nuclear localization of PARP-1 and AIF. Furthermore, low-dose curcumin combined with ultraviolet B (UVB) irradiation synergistically induced parthanatos in DLBCL cells. Notably, olaparib, a specific PARP-1 inhibitor, attenuated activation of parthanatos induced by curcumin alone or in combination with UVB. In summary, the present findings suggest that curcumin inhibits DLBCL cell proliferation through PARP1-mediated parthanatos and exhibits synergistic effects with UVB irradiation.