title: Repositioning "old" drugs for new causes: identifying new inhibitors of prostate cancer cell migration and invasion.
abstract: The majority of prostate cancer (PCa) deaths occur due to the metastatic spread of tumor cells to distant organs. Currently, there is a lack of effective therapies once tumor cells have spread outside the prostate. It is therefore imperative to rapidly develop therapeutics to inhibit the metastatic spread of tumor cells. Gain of cell motility and invasive properties is the first step of metastasis and by inhibiting motility one can potentially inhibit metastasis. Using the drug repositioning strategy, we developed a cell-based multi-parameter primary screening assay to identify drugs that inhibit the migratory and invasive properties of metastatic PC-3 PCa cells. Following the completion of the primary screening assay, 33 drugs were identified from an FDA approved drug library that either inhibited migration or were cytotoxic to the PC-3 cells. Based on the data obtained from the subsequent validation studies, mitoxantrone hydrochloride, simvastatin, fluvastatin and vandetanib were identified as strong candidates that can inhibit both the migration and invasion of PC-3 cells without significantly affecting cell viability. By employing the drug repositioning strategy instead of a de novo drug discovery and development strategy, the identified drug candidates have the potential to be rapidly translated into the clinic for the management of men with aggressive forms of PCa.
authors.affiliation: Australian Prostate Cancer Research Centre-Queensland, School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia.|Translational Research Institute, Brisbane, Australia.
authors.forename: Esha T
authors.initials: ET
authors.lastname: Shah
authors.affiliation: Australian Prostate Cancer Research Centre-Queensland, School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia.|Translational Research Institute, Brisbane, Australia.
authors.forename: Akanksha
authors.initials: A
authors.lastname: Upadhyaya
authors.affiliation: Australian Prostate Cancer Research Centre-Queensland, School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia.|Translational Research Institute, Brisbane, Australia.
authors.forename: Lisa K
authors.initials: LK
authors.lastname: Philp
authors.affiliation: Australian Prostate Cancer Research Centre-Queensland, School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Tang
authors.affiliation: The University of Queensland Diamantina Institute, University of Queensland, Brisbane, Australia.|Translational Research Institute, Brisbane, Australia.
authors.forename: Dubravka
authors.initials: D
authors.lastname: Skalamera
authors.affiliation: Australian Prostate Cancer Research Centre-Queensland, School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia.|Translational Research Institute, Brisbane, Australia.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Gunter
authors.affiliation: Australian Prostate Cancer Research Centre-Queensland, School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia.|Translational Research Institute, Brisbane, Australia.
authors.forename: Colleen C
authors.initials: CC
authors.lastname: Nelson
authors.affiliation: Australian Prostate Cancer Research Centre-Queensland, School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia.|Translational Research Institute, Brisbane, Australia.
authors.forename: Elizabeth D
authors.initials: ED
authors.lastname: Williams
authors.affiliation: Australian Prostate Cancer Research Centre-Queensland, School of Biomedical Sciences, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia. b.hollier@qut.edu.au.|Translational Research Institute, Brisbane, Australia. b.hollier@qut.edu.au.
authors.forename: Brett G
authors.initials: BG
authors.lastname: Hollier
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D008297:Male; D009361:Neoplasm Invasiveness / Q000473:pathology; D009362:Neoplasm Metastasis / Q000188:drug therapy* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents
keywords: Drug repositioning; IncuCyte™; Migration; PC-3; Prostate cancer; Scratch wound assay