Table 1.

Summary table of the drugs that have been repurposed to be used in prostate cancer in pre-clinical models.

Ref.	Drug	Original Indication	PCa Cell Lines Targeted	In Vivo Studies	Mode(s) of Action	Effect(s)
[137]	Propranolol	Anti-hypertensive	-	-	Blockade of beta-2 receptors Inhibition of PAP of lipins	Halted PCa proliferation Promoted autophagy vesicles and hence cancer cell death
[138]	Digoxin	Anti-arrhythmic			Inhibition of Na+/K+ ATPase pump which increases intracellular Ca2+ levels
[138,139]	Ouabain	Anti-arrhythmic	PPC-1	Male SCID		Sensitize PPC-1 to anoikis, normal apoptosis via detachment from ECM
[140]	Aspirin	Anti-inflammatory	LNCaP		Inhibition of cyclooxygenase (COX) pathway Decreased PG production Reduction of cyclin D1	Promote antitumerogenic effects in combination with statins
[141]	Celecoxib	Anti-inflammatory	LNCaP & androgen-nonresponsive PC-3	LNCaP in bovine brain extracts	Selective COX-2 blockade Blockade of Akt pathway	Induction of apoptosis
[142]	dexamethasone	Anti-inflammatory	DU145 PCa cells		Decreased production of inflammatory mediators Inhibit ERG, an oncogene	Decreased proliferation of PCa in an in silico model via ERG inhibition
[143,144,145]	Simvastatin	Anti-hyperlipidimic	PC3, 22Rv1, DU145, DU145R80, LNCaP prostate cancer cell lines and EPN normal prostate epithelial cells	DU145R80, 22Rv1 parental and docetaxel resistant cells in xenografts	Inhibition of HMG-CoA reductase	Sensitization of PCa cells to docletaxil in combination with valproic acid via YES inhibition Promotion of apoptosis via cholesterol depletion Sensitization of anti-androgen resistant CRPC
[146,147,148]	Metformin	Anti-diabetic			Increased sensitivity to insulin inhibiting hepatic production of glucose Restriction of hepatic gluconeogenesis	Decreased growth, proliferation and differentiation by downregulating PI3K axis Decreased ARs, acting as an adjunct to ADT
[149]	Glipizide	Anti-diabetic	PC-3, 22Rv1 and DU145 PC	TRAMP transgenic mouse model	Stimulation of β-cell insulin secretion	Inhibition of angiogenesis by targeting HMGIY/ANGPT1 pathway
[150]	Mebendazole	Anti-helminthic	LNCaP		Inhibition of microtubule assembly	Promoting cell death in synergism with docletaxel
[151]	Niclosamide	Anti-helminthic	LNCaP, VCaP, CWR22Rv1, PC3 and HEK293	CWR22Rv1 cells in SCID mice	Unclear; uncoupling of oxidative phosphorylation chain	sensitize treatment to enzalutamide by decreasing AR-V7
[152,153]	Nelfinavir	Anti-retroviral	DU145 and PC3 cell lines		Inhibition of proteases	Combatted CRPC by inhibiting Site-2 Protease (S2P) cleavage and Regulated Intramembrane Processing (RIP)
[154]	CMT-3	Anti-microbial	Many lines	xenografts of PC-3 tumors	Inhibition of protein synthesis	Promoted apoptosis in PCa cell lines via activation of caspase-3 and caspase-9
[155]	Zoledronic acid	Bisphosphonate	LuCaP 23.1, a PSA-producing human CaP xenograft	LuCaP 23.1, a PSA-producing human CaP xenograft	Inhibition of bone resorption via inhibition of osteoclast activity	Decreased metastatic potential in vivo and induced G1 arrest, proliferation decline and apoptosis in vitro
[156]	Valproic acid	Anti-epileptic	AR-positive (LNCaP and C4-2) and AR-negative (DU145 and PC3)	LNCaP, C4-2, and DU145 Xenograft models	Inhibition class I histone deacetylases (HDAC)	Reduced PCa cellular proliferation and upregulated caspase-2 and caspase-3 activity
[157]	Mifepristone	Anti-progestational steroid			Anti-progesterone with potent progesterone receptor (PR) affinity	Promotion of anti-cancer effects in both androgen sensitive and insensitive PCa, via induction of TFG-beta 1, a pro-apoptotic TF

Abbreviations: AR: androgen receptor; COX: cyclooxygenase; CRPC: castration-resistant prostate cancer; ECM: extracellular matrix; PCa: prostate cancer; PR: progesterone receptor; SCID: severe combined immunodeficiency.