Biological Activity
arylquin 1 is a potent secretagogue of the tumor suppressor protein prostate apoptosis response-4 (par-4).par-4 is ubiquitously expressed in normal cells and tissues, but it is inactivated, downregulated or mutated in several types of cancers. par-4 can selectively induce cancer cell apoptosis but not normal cells. both intracellular and secreted par-4 have a role in apoptosis induction by caspase-dependent mechanisms.
in vitro
previous study showed that arylquin 1 produced a dose-dependent secretion in mef cells and also induced robust secretion of par-4 in normal or immortalized human cells but failed to induce the secretion of par-4 in various lung tumor cells. moreover, it was found that brefeldin a, which blocked anterograde endoplasmic reticulum–golgi traffic, could inhibit basal and arylquin 1–inducible par-4 secretion, indicating that arylquin 1 regulated par-4 secretion through the classical secretory pathway. in addition, cells treated with arylquin 1 showed neither par-4 co-immunoprecipitation nor colocalization with vimentin, suggesting that arylquin 1 could displace par-4 from vimentin. this action of arylquin 1 was not associated with inhibition of vimentin expression, demonstrating that arylquin 1 might cause conformational changes in vimentin to block its ability to bind and sequester par-4 [1].
