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.