Cyathus striatus Extract Induces Apoptosis in Human Pancreatic Cancer Cells and Inhibits Xenograft Tumor Growth In Vivo

SIMPLE SUMMARY: The main aim of the present study is to test the effect of Cyathus striatus extract on the cell growth of human pancreatic cancer cells in vitro and in vivo. In addition, the effect of the extract on the gene expression was detected. The results indicated that Cyathus striatus extract significantly inhibited the cell viability and induced apoptosis. The treatment of xenograft mice harboring human pancreatic cancer cells significantly inhibited tumor growth through the induction of apoptosis. RNAseq experiments revealed the involvement of the MAPK and P53 signaling pathways and pointed toward endoplasmic reticulum stress induced apoptosis. These results may suggest that Cyathus striatus extract may contain pro-apoptotic factors that can be identified and used for the treatment of human cancer. ABSTRACT: Pancreatic cancer is a highly lethal disease with limited options for effective therapy and the lowest survival rate of all cancer forms. Therefore, a new, effective strategy for cancer treatment is in need. Previously, we found that a culture liquid extract of Cyathus striatus (CS) has a potent antitumor activity. In the present study, we aimed to investigate the effects of Cyathus striatus extract (CSE) on the growth of pancreatic cancer cells, both in vitro and in vivo. The proliferation assay (XTT), cell cycle analysis, Annexin/PI staining and TUNEL assay confirmed the inhibition of cell growth and induction of apoptosis by CSE. A Western blot analysis demonstrated the involvement of both the extrinsic and intrinsic apoptosis pathways. In addition, a RNAseq analysis revealed the involvement of the MAPK and P53 signaling pathways and pointed toward endoplasmic reticulum stress induced apoptosis. The anticancer activity of the CSE was also demonstrated in mice harboring pancreatic cancer cell line-derived tumor xenografts when CSE was given for 5 weeks by weekly IV injections. Our findings suggest that CSE could potentially be useful as a new strategy for treating pancreatic cancer.