Description
Canthardin is a toxin initially produced by the blister beetle, Canarthis vesicatoria. Canthardin competitively inhibits serine/threonine phosphatases such as protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A). Canthardin exhibits anticancer and anti-resorptive activities. In cancer cells, canthardin upregulates expression of caspase 1 and the NGF receptor and downregulates expression of Bcl-2-like protein 10, Fas ligand, and TNF-α. In colorectal cancer cells, canthardin inhibits heat shock factor 1 and downstream HSP70- and BAG3-related signaling, inhibiting cell proliferation. Additionally, cantharidin displays pro-inflammatory activity in vivo, producing increases in MCP-1, IL-6, IL-1β, and myeloperoxidase. In vitro, this compound inhibits RANKL-induced expression of Fra-2 and cathepsin K and inhibits activation of ERK and MAPK signaling; these actions result in inhibition of differentiation and resorptive activity.