Synthetic and natural compounds regulate activity of ABCC6 transporter

SIB 2019 Synthetic and natural compounds regulate activity of ABCC6 transporter DEPARTMENT OF SCIENCES- UNIVERSITY OF BASILICATA, Potenza, Italy *CORRESPONDING AUTHOR: angela.ostuni@unibas.it ATP-binding cassette transporters (ABC transporters) are members of a superfamily consisting of 49 proteins that transport a wide variety of substrates across extra- and intracellular membranes by using energy released from ATP hydrolysis [1]. Mutations in ABC genes underlie at least 19 human genetic disorders [2]. Many transporters are involved in the multidrug resistance, that is the failure due to the reduction of cellular accumulation of drugs. Many ABC transporters inhibitors have been proposed as molecules able to reverse multidrug resistance in cancer cells [3]. ABCC6 is a member of ABCC family poorly involved in drug resistance whose mutations are associated to the Pseudoxanthoma elasticum (PXE), an autosomal recessive disease characterized by a progressive ectopic calcification [4]. Although the substrate transported is not known, ABCC6 has been shown to promote ATP release [5]. In this study we evaluate the effects of both probenecid, an uricosuric drug and quercetin, a nonterpenoid secondary metabolite on HepG2 cells. Both are known broad spectrum inhibitors of ABC transporters. The observed effects are all reversed by the addition of ATP suggesting the involvement of the ABCC6 protein. FUNDED BY INBIOMED PROJECT (MIUR, ARS01_01081) [1] S. Wilkens. (2015) F1000Prime Rep. 7, 14. [2] V. Vasiliou, K. Vasiliou, DW. Nebert (2009) Hum Genomics. 3(3):281-90. [3] F. Cuviello, F. Bisaccia, D. Spinelli, et al. (2019) Eur J Med Chem 164 1-7. [4] F. Martinelli, F. Cuviello, MC Pace et al. (2018) Cells. Front. Mol. Biosci., 5:75. [5] RS Jansen, S. Duijst, S. Mahakena, et al. . (2014) Arterioscler. Thromb. Vasc. Biol. 34, 1985–1989