Pithecellobium dulce induces apoptosis and reduce tumor burden in experimental animals via regulating pro-inflammatory cytokines and anti-apoptotic gene expression

Abstract

The present study demonstrates the efficacy of fruit extract of Pithecellobium dulce (FPD) against Dalton's lymphoma ascites (DLA) cell lines in vitro and in vivo (DLA induced ascitic and solid tumor). Administration of FPD induced apoptosis in DLA cells via p53 regulation both in vitro and in vivo. Cell viability was quantified by MTT assay. Apoptotic cells were determined by qualitative (staining methods) and quantitative analysis (Annexin-propidium iodide based flow cytometry). Expression of pro-apoptotic markers (Caspase 3, Caspase 9, and Bax) were markedly elevated, while expression of anti-apoptotic proteins (Bcl 2 and Bcl XL) were downregulated in tumor cells. FPD administration effectively reduced tumor burden, increased mean survival time via modulating NF-kB, and reduced the level of proinflammatory cytokines (IL-6, IL-1β, GM-CSF and TNF-α). Phytochemical screening of FPD by GC/MS analysis divulged the presence of several novel bioactive chemical constituents. Further, bioactive components identified from extract were evaluated for drug-like properties by Lipinski rule of five and properties. Naringenin, nootkatone, and gallic acid showed good drug-like properties and good pharmacokinetic profiles compared to other bioactive constituents in the extract.