The presence of a fused 5/6/7 tricyclic core characterizes the group of
cyathane diterpene natural products, that include more than 170 compounds, isolated from fungi such as Cyathus africanus and Hericium erinaceus. These compounds have a common biosynthetic precursor (cyatha-3,12-diene) and can be produced bio- or hemi-synthetically, or via total syntheses.
Cyathane diterpenes display a range of pharmacological properties, including anti-inflammatory (possibly through binding to the iNOS
protein) and
neuroprotective effects. Many cyathanes like cyahookerin C, cyathin Q and cyafranines B and G can stimulate neurite outgrowth in cells, whereas conversely a few molecules (such as
scabronine M) inhibit
NGF-stimulated neurite outgrowth. The main anticancer cyathanes are
erinacine A and
cyathins Q and R, with a capacity to trigger
cancer cell death dependent on the production of
reactive oxygen species (ROS). These compounds, active both in vitro and in vivo, activate different signaling pathways in
tumor cells to induce apoptosis (and autophagy) and to upregulate the expression of several
proteins implicated in the organization and functioning of the actin cytoskeleton. An analysis of the functional analogy between
erinacine A and other natural products known to interfere with the actin network in a ROS-dependent manner (notably
cucurbitacin B) further supports the idea that
erinacine A functions as a perturbator of the cytoskeleton organization. Collectively, we provide an overview of the molecular diversity of
cyathane diterpenes and the main mechanisms of action of the lead compounds, with the objective to encourage further research with these fungal products. The anticancer potential of
erinacine A deserves further attention but it will be necessary to better characterize the implicated targets and signaling pathways.