TEOA Inhibits Proliferation And Induces DNA Damage Of Diffuse Large B-cell Lymphoma Cells Through Activating ROS Dependent P38 MAPK Signaling Pathway

Objective Diffuse large B-cell lymphoma(DLBCL)is the most common subtype of lymphoma,accounting for 30% ~ 40% of non-Hodgkin’s lymphomas(NHL).With the administration of rituximab,the outcomes of DLBCL are improved significantly.But,the unavoidable development of resistance limits the long-term efficacy.Therefore,a new generation of less toxic and higher chemotherapy response is needed to prevent or reverse chemoresistant.TEOA is a pentacyclic triterpenoid compound and isolated from the roots of Actinidiaeriantha.Studies confirmed that TEOA had significant cytotoxicity on gastrointestinal cancer cells.However,there is no relevant report on DLBCL cells.In this study,we investigated the underlying molecular mechanism of the anticancer activity of TEOA in DLBCL cells.Methods The growth inhibitory effect of TEOA was evaluated by CCK-8 Assay.The cell apoptosis and reactive oxygen species(ROS)were determined by flow cytometry.DNA damage was performed by cellular immunohistochemistry.The potential mechanisms for proteins level in apoptosis,DNA damage and P38 MAPK pathway were analyzed by Western Blot.Results Ours results demonstrated that TEOA inhibited proliferation and induced apoptosis in time-and dose-dependent manners.TEOA induced ROS generation,which was reversed by N-acetyl cysteine(NAC).TEOA induced DNA damage and increased the expression of γ-H2 AX,phosphorylation of Chk1 and Chk2.Likewise,TEOA induced the activation of p38 MAPK pathway and increased the level of phosphorylation p38.Furthermore,TEOA-induced DNA damage was rescued by p38 inhibitor SB20358 and NAC.Conclusion TEOA has a significant anti-tumor effect on diffuse large B-cell lymphoma cells.DNA damage and P38 MAPK pathway may be involved in the anti-tumor mechanism of TEOA.The combination of TEOA and cyclophosphamide,vindesine to treat diffuse large B-cell lymphoma is meaningful and feasible.