Tumor suppression activity of bioactive components from Phomopsis sp. endophyte isolated from Ligustrum liukuensis Koidz

Abstract

Endophytic symbionts are involved in the production of bioactive secondary metabolites in medicinal plants. In this study, EN‐032601, an endophyte from seeds of Ligustrum liukuensis Koidz, was indicated to Phomopsis sp. after 18s rDNA sequence. Cultivated metabolites and isolated compounds were used to evaluate their tumor suppression effect. The broth extracts (YHC1‐200‐2) and anthraquinones (YHC2‐81‐X) from EN‐032601 showed differential cancer cell cytotoxicity. The tumor suppression effect was observed after YHC1‐200‐2 treatment using H460 xenograft model. Body weight loss was not observed. Blood cell composition, hematopoietic parameters, bone marrow cells and spleen/total BW were not altered indicating the safety of this component. Among those anthraquinones, compound YHC2‐81‐3 arrested cell cycle in G2/M phase and gradually induced apoptosis. Cell‐cycle related proteins including induction of cyclin B1, pMPM‐2, p Cdk1 and pCdc25C, and suppression of cyclin E, cyclin A and p27 (a Cdk inhibitor) were observed. Apoptotic proteins alternation was observed including decrease of Bcl‐2 and Bcl‐xl, increase of Bax, activation of caspase 3 and PARP cleavage. Further, YHC2‐81‐3 enhanced the cytotoxic sensitivity of cispatin on H460 cells. Further, YHC2‐81‐3 showed strong DNA damaging property (induce DNA fragmentation and tailing of comet assay) and also impaired the DNA repair gene expression (ATR and ATM). In summary, these results indicated these metabolites might participate in attenuation of cancer progress toward development of targeting therapeutic agents.