Parthenolide is a
sesquiterpene lactone compound isolated from the leaves and flowerheads of the plant feverfew (Tanacetum parthenium). The anticancer effects of
parthenolide have been well studied and this
lactone compound is currently under clinical trials.
Parthenolide is also a
protective agent in cardiac
reperfusion injury via its inhibition of nuclear factor-κB (NF-κB). Not much is known if this compound affects signal transduction in non-
tumor cells. We investigated whether
parthenolide affected Ca(2+) signaling in endothelial cells, key components in regulating the vascular tone. In this work using mouse cortical microvascular bEND.3 endothelial cells, we found that a 15-h treatment with
parthenolide resulted in amplified
ATP-triggered Ca(2+) signal; the latter had a very slow decay rate suggesting suppression of Ca(2+) clearance. Evidence suggests
parthenolide suppressed Ca(2+) clearance by inhibiting the plasmalemmal Ca(2+) pump; such suppression did not result from decreased expression of the plasmalemmal Ca(2+) pump
protein. Rather, such suppression was possibly a consequence of endoplasmic reticulum (ER) stress, since
salubrinal (an ER stress protector) was able to alleviate
parthenolide-induced Ca(2+) clearance suppression. Given the current deployment of
parthenolide as an anti-
cancer drug in clinical trials and the potential usage of this
lactone as a cardioprotectant, it is important to examine in details the perturbing effects of
parthenolide on Ca(2+) homeostasis in endothelial cells and neighboring vascular smooth muscle cells, activities of which exert profound effects on hemodynamics.