Repositioning “old” drugs for new causes: identifying new inhibitors of prostate cancer cell migration and invasion

Shah, Esha T., Upadhyaya, Akanksha, Philp, Lisa K., Tang, Tiffany, Skalamera, Dubravka, Gunter, Jennifer, Nelson, Colleen C., Williams, Elizabeth D. and Hollier, Brett G. (2016) Repositioning “old” drugs for new causes: identifying new inhibitors of prostate cancer cell migration and invasion. Clinical and Experimental Metastasis, 33 4: 385-399. doi:10.1007/s10585-016-9785-y


Author Shah, Esha T.
Upadhyaya, Akanksha
Philp, Lisa K.
Tang, Tiffany
Skalamera, Dubravka
Gunter, Jennifer
Nelson, Colleen C.
Williams, Elizabeth D.
Hollier, Brett G.
Title Repositioning “old” drugs for new causes: identifying new inhibitors of prostate cancer cell migration and invasion
Journal name Clinical and Experimental Metastasis   Check publisher's open access policy
ISSN 1573-7276
0262-0898
Publication date 2016-04
Year available 2016
Sub-type Article (original research)
DOI 10.1007/s10585-016-9785-y
Open Access Status Not Open Access
Volume 33
Issue 4
Start page 385
End page 399
Total pages 15
Place of publication Dordrecht, Netherlands
Publisher Springer Netherlands
Collection year 2017
Language eng
Formatted 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.
Keyword Drug repositioning
IncuCyte™
Migration
PC-3
Prostate cancer
Scratch wound assay
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
UQ Diamantina Institute Publications
 
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