Cyclo(L-Phe-trans-4-hydroxy-L-Pro) (Cyclo(L-phenylalanyl-trans-4-hydroxy-L-proline)) is a natural product found in Phellinus igniarius.

We previously identified Streptomyces griseus as an anti-cancer agent (Kim et al., 2014). In this study, we isolated compounds from S. griseus and evaluated their anticancer effect and toxicity in vitro and in vivo. METHODS AND RESULTS: Preparative centrifugal partition chromatography (CPC) was used to obtain three compounds, cyclo(L-[4-hydroxyprolinyl]- L -leucine], Cyclo(L-Phe-trans-4-hydroxy-L-Pro) and phenethyl acetate (PA). We chose PA, which had the highest anticancer activity, as a target compound for further experiments. PA induced the formation of apoptotic bodies, DNA fragmentation, DNA accumulation in G0/G1 phase, and reactive oxygen species (ROS) formation. Furthermore, PA treatment increased Bax/Bcl-xL expression, activated caspase-3, and cleaved poly-ADP-ribose polymerase (PARP) in HL-60 cells. Simultaneous evaluation in vitro and in vivo, revealed that PA exhibited no toxicity in Vero cells and zebrafish embryos. CONCLUSIONS: We revealed, for the first time, that PA generates ROS, and that this ROS accumulation induced the Bcl signaling pathway[1].