Natural products deriving from plants used in traditional medicine are an important source of anti-cancer agents. Our study focuses on Metaxya rostrata C.Presl (Metaxyaceae), a tree fern widespread in the rainforests of Central and South America, that is administered against intestinal ulcers and tumors in ethnic medicine. Colorectal cancer is among the most common malignant diseases in the western world and the search for effective new therapeutics is an ongoing task. An activity-guided study of Metaxya rostrata led to the isolation of two structurally related xanthones: 2-deprenyl-rheediaxanthone B (XB) and 2-deprenyl-7-hydroxy-rheediaxanthone B (OH-XB). Our previous work demonstrated that XB causes cell death in colon carcinoma cell lines via the mechanism of mitotic catastrophe [1].
First results of the cytotoxic activity of OH-XB on SW480 cells by neutral red uptake assay indicated that this compound is at least as active as XB. The IC50 concentrations for dose-dependent cell loss were calculated to be 5.3±1.0µM for OH-XB and 6.7±1.2µM for XB. Cell cycle distribution was assessed by FACS analysis and demonstrated an OH-XB-induced S-phase cell cycle arrest in contrast to XB-incubated cells, which accumulated in G2-M-phase. Analysis by western blot confirmed a cell cycle blockade in S-phase by decreased levels of cyclins A and B, while cyclin E increased. Also in contrast to XB, treatment with OH-XB caused morphological modifications typical for classical apoptosis. This is substantiated by increased caspase activity and enhanced cleavage of PARP. Additional xanthones are currently isolated in order to determine a detailed structure-activity relationship. This work resulted already in a further new natural compound from Metaxya rostrata, a methylated derivative of OH-XB, which is under testing.
[1] Kainz KP, Krenn L, Erdem Z, Kaehlig H, Zehl M, Bursch W, Berger W, Marian B. PloS ONE 2013; 8(6): e65745.