Inhibition of the Lysophosphatidylinositol Transporter ABCC1 Reduces Prostate Cancer Cell Growth and Sensitizes to Chemotherapy

Aikaterini Emmanouilidi; Ilaria Casari; Begum Gokcen Akkaya; Tania Maffucci; Luc Furic; Federica Guffanti; Massimo Broggini; Xi Chen; Yulia Y Maxuitenko; Adam B Keeton; Gary A Piazza; Kenneth J Linton; Marco Falasca

doi:10.3390/cancers12082022

Inhibition of the Lysophosphatidylinositol Transporter ABCC1 Reduces Prostate Cancer Cell Growth and Sensitizes to Chemotherapy

Cancers (Basel). 2020 Jul 23;12(8):2022. doi: 10.3390/cancers12082022.

Authors

Aikaterini Emmanouilidi¹, Ilaria Casari¹, Begum Gokcen Akkaya², Tania Maffucci², Luc Furic^{3

4

5}, Federica Guffanti⁶, Massimo Broggini⁶, Xi Chen⁷, Yulia Y Maxuitenko⁷, Adam B Keeton⁷, Gary A Piazza⁷, Kenneth J Linton², Marco Falasca^{1

2}

Affiliations

¹ Metabolic Signalling Group, School of Pharmacy and Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, WA 6102, Australia.
² Centre for Cell Biology and Cutaneous Research, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK.
³ Prostate Cancer Translational Research Laboratory, Peter MacCallum Cancer Centre, Melbourne, VI 3000, Australia.
⁴ Cancer Program, Biomedicine Discovery Institute and Department of Anatomy and Developmental Biology, Monash University, Clayton, VI 3800, Australia.
⁵ Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VI 3010, Australia.
⁶ Laboratory of Molecular Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milan, Italy.
⁷ Drug Discovery Research Center, USA Health Mitchell Cancer Institute, Mobile, AL 36604-1405, USA.

Abstract

Expression of ATP-binding cassette (ABC) transporters has long been implicated in cancer chemotherapy resistance. Increased expression of the ABCC subfamily transporters has been reported in prostate cancer, especially in androgen-resistant cases. ABCC transporters are known to efflux drugs but, recently, we have demonstrated that they can also have a more direct role in cancer progression. The pharmacological potential of targeting ABCC1, however, remained to be assessed. In this study, we investigated whether the blockade of ABCC1 affects prostate cancer cell proliferation using both in vitro and in vivo models. Our data demonstrate that pharmacological inhibition of ABCC1 reduced prostate cancer cell growth in vitro and potentiated the effects of Docetaxel in vitro and in mouse models of prostate cancer in vivo. Collectively, these data identify ABCC1 as a novel and promising target in prostate cancer therapy.

Keywords: ABC transporter; ABCC1/MRP1; Docetaxel; lysophosphatidylinositol; prostate cancer.

Grants and funding

PG12-23/PCUK_/Prostate Cancer UK/United Kingdom