Vulpinic acid contributes to the cytotoxicity of Pulveroboletus ravenelii to human cancer cells by inducing apoptosis†
Pulveroboletus ravenelii (Berk. et Curt.) Murr. (Boletaceae), commonly known as Ravenel's bolete, is an edible mushroom that is widely distributed in Korea, Japan, and China. P. ravenelii is used in traditional Chinese medicine and also to create color dyes. In this study, we explored the pharmacological activity of the fruiting bodies of P. ravenelii and found that their MeOH extracts showed cytotoxic activity in vitro against a variety of human cancer cells, including four lung adenocarcinoma cell lines (A549, NCI-H1264, NCI-H1299, and Calu-6), two pancreatic ductal adenocarcinoma cell lines (PANC-1 and MIA PaCa-2), and a hepatocellular carcinoma cell line (Hep G2), by inducing apoptosis. Based on the bioactivity-guided fractionation to identify the fraction with the highest cytotoxic activity, chemical investigation of the MeOH extract of the fruiting bodies of P. ravenelii led to the isolation of vulpinic acid (VA) (1) as the main component of the most cytotoxic fraction, the hexane-soluble fraction. Treatment with VA significantly reduced cell viability by inducing apoptotic cell death in all human cancer cell lines tested, with IC50 values ranging from 21.65 to 146.17 μM. These findings provide experimental evidence for a novel biological activity of P. ravenelii against human cancer cells. We also identified VA as the main constituent that contributes to the cytotoxic activity of P. ravenelii, thus raising the possibility of using P. ravenelii as a functional food as well as a source of lead compounds for the development of novel drugs for cancer prevention and management.