(-)-Dehydrocostus lactone

Suppressors of cytokine signaling (SOCS) proteins negatively regulate cytokine receptor signaling. The SOCS family include eight members SOCS-1 to SOCS-7 and CIS. Dehydrocostus lactone (DHE) is a sesquiterpene lactone extracted from Saussurea lappa and Aucklandia lappa. The compound possesses antifungal and antimycobacterial activity and exhibit a cytotoxic effect against HepG2, OVCAR-3, and HeLa cell lines. DHE inhibits cell proliferation not only in early-stage breast cancer MCF-7 but also in more advanced stage MDA-MB-231 cancer cells, without significant effect on H184B5F5/M10 normal mammary epithelial cells. The inhibition of breast cancer cells proliferation occurs through cell cycle blockade and apoptosis. DHE inhibits cell cycle progression and cell death through SOCS-1 and SOCS-3. Dehydrocostus lactone forms a chemical-synthetic lethal combination with subinhibitory doses of a FolE2 inhibitor trimethoprim in pathogen Burkholderia pseudomalle without annihilating the gut′s essential bacteria.