Pithecellobium dulce inhibits pulmonary metastasis induced by B16F10 melanoma cells in C57BL/6 via regulating EGFR/STAT/ NFκB /AKT signaling axis.

Abstract

In this present study we analyzed anti-metastatic efficacy of fruit extract of Pithecellobium dulce (FPD) against B16F10 induced pulmonary metastatic model. FPD administration significantly (p < .01) reduced lung fibrosis, as evidenced by histochemical collagen analysis by Masson's trichome staining, total collagen, hexosamine, and uronic acid. Results showed that FPD treatment significantly attenuated the expression of EGFR mediated P38 and STAT1/3 expression, thus reduced NFκB mediated signaling cascade. Further, the expression of PIP3CA mediated activation of the AKT survival signaling pathway has been analyzed. Interestingly, in FPD treated group, the expression of AKT pathway has also downregulated. Further, we analyzed the downstream regulators of NFκB and AKT signaling pathways, which include, inflammatory genes (iNOS, COX2, NFκB, TGFβ1, IL5, IL1β, IFNγ, IL6, IL10, MCP1, GMCSF), anti-apoptotic genes (BCL2 and BCLXL), cell cycle regulators (cyclin D1 and Ki67), fibrosis activator (CT1α1), angiogenesis promoter (VEGF), metastatic promoter (MMP2/9, N CADH), mucin (MUC5AC), pro-apoptotic genes (Bax, CAS3 and CAS9) and metastasis inhibitors (TIMP1/2, E CADH, p53, PTEN). The expression of inflammatory, anti-apoptotic, cell cycle regulators, fibrosis activator, angiogenesis and metastasis promoter, and mucins were markedly reduced by FPD administration. Interestingly, the level of expression of anti-metastatic genes were markedly elevated in FPD administrated group. Lung histopathology further confirmed the anti-metastatic efficacy of FPD. PRACTICAL APPLICATIONS: Different parts of P. dulce has long been used as a folklore medicine against different diseases. This study demonstrated that bioactive constituents present in the fruit extract of P. dulce (FPD) significantly attenuated proliferation via regulating EGFR/STAT/NFκB/AKT signaling axis.