Table 1.

Effects of curcumin in vitro and in vivo.

Model	Cell Lines/Drugs	Outcome	Mechanism	Reference
	COMBINATION THERAPY
in vitro	T24-gemcitabine resistant GCB + Curcumin	reversal of drug resistance	ABCC2; Cleaved PARP ↑ DCK; TK1;TK2; Migration ↓	[87]
in vitro	IFN-α–sensitive (RT4V6) and IFN-α–resistant (KU-7) GCB + Curcumin	increased apoptosis, IFN-α-independent	NF-κB ↓	[88]
in vitro	253J-Bv and T24 Cisplatin + Curcumin	increased apoptosis	Caspase-3; ROS ↑ p-MEK; p-ERK1/2 ↑	[90]
in vivo	nude mice, 253J-Bv xenografts Cisplatin + Curcumin	decreased tumor size	-	[90]
in vitro	253J-Bv BCG + Curcumin	increased apoptosis	TRAIL ↑; TRAIL receptor activity ↑; NF-κB ↓	[81]
in vivo	MTB-2-transplanted C3H mice BCG + Curcumin	increased apoptosis, decreased tumor size	Ki-67; CD31; NF-κB ↓; Cyclin D1; VEGF; COX-2 ↓ c-myc; Bcl-2 ↓ TRAIL receptor ↑	[81]
in vivo	F344 rats, AY27 xenografts BCG + Cyclodextrin–Curcumin	lower tumor stage	-	[80]
	MONOTHERAPY
in vitro	253JB-V and KU7	increased apoptosis, cell growth inhibition	Sp1; Sp3; Sp4; Survivin ↓ VEGF; VEGFR1; p21; p27↓ Cleaved PARP ↑	[34]
in vivo	nude mice, KU7 xenografts	decreased tumor growth	Sp1; Sp3; Sp4 ↓	[34]
in vitro	5637 and WH	decreased cell viability, proliferation blockade	KLF5; YAP; TAZ; AXL ↓ ITGB2; CDK6; CYR61 ↓	[45]
in vivo	Nude mice, 5637 xenografts	decreased tumor size	YAP/TAZ; KLF5;PCNA ↓ Cyclin D1 ↓	[45]
in vitro	AY-27 (rat) and T-24,	increased apoptosis, cell cycle arrest	7-AAD; p27; Caspase-3 ↑ Cyclin D1; pRb-P; cyclin E ↓ p21; p53; NF-κB ↓	[47]
in vitro	T24	inhibited cell growth, G2/M arrest	Cyclin A; COX-2, PGE2 ↓ p21 ↑	[33]
in vitro	T24 and 5637	decreased cell growth, increased apoptosis, inhibition of migration	Caspase-3/7; TIMP-2 ↑ MMP-2; MMP-9 ↓	[53]
in vitro	T24 and 5637	proliferation blockade, increased apoptosis inhibition of migration and invasion	β-Catenin ↓ Vimentin ↓ N-cadherin ↓ E-cadherin ↑	[61]
in vitro	T24, UMUC2 and EJ	decreased cell viability, increased apoptosis, G2/M cell cycle arrest	Bcl-2; Survivin ↓ Bax; p53 ↑	[31]
in vivo	Wistar rats, N-methyl-N-nitrosourea-induced bladder cancer	increased apoptosis	Nuclear condensation and fragmentation ↑	[31]
in vitro	EJ	decreased cell viability, increased apoptosis	Intracellular esterase activity ↑ Caspase-3 ↑ DNA fragmentation ↑	[57]
in vitro	T24	decreased cell growth, G2/M cell cycle arrest	Aurora A ↓	[31]
in vitro	T24	decreased benzidine-triggered cell proliferation and G1 to S phase transition	p-ERK1/2 ↓ PCNA ↓ Cyclin D1 ↓ p21 ↑	[42]
in vitro	UMUC3 and EJ	proliferation blockade, increased apoptosis	PCNA; cyclin D1; Bcl-2 ↓ Bax; Cleaved Caspase 3 ↑ Caspase 8; Caspase 9 ↑	[56]
in vitro	5637 and BFTC 905	decreased cell viability, inhibition of invasion	MMP-2; MMP-9 ↓ ROS; HO-1 ↑	[66]
in vivo	C57BL/6 mice, MB49 xenograft		HO-1 ↑	[66]
in vitro	T24 and RT4	proliferation blockade, increased apoptosis, inhibition of mobility, G2/M cell cycle arrest	Trop2 ↓ Cyclin E1 ↓ p27 ↑	[30]
in vitro	T24 and SV-HUC-1	inhibition of invasion, increased apoptosis	miR-7641 ↓ p16 ↑	[49]
in vitro	T24 Combination with irradiation	decreased cell viability and colony formation	miR-1246 ↓	[50]
in vitro	T24	proliferation blockade, increased apoptosis	miR-203 ↑ Akt2; Src ↓	[48]
in vitro	RT112, TCCSUP and UMUC3 Combination with visible light	alteration in adhesion, inhibition of chemotaxis	RT112: pFAK; α5; β1 ↓ TCCSUP: α3; α5; β1 ↓ UMUC3: pFAK; α5; β1 ↓	[59]
in vivo	BALB/c mice exposed to tobacco smoke for 12 weeks	ameliorated EMT alterations	p-ERK1/2; p-JNK ↓ p-p38 MAPK; E-cadherin ↓ N-cadherin; ZO-1; Vimentin ↓	[62]
in vivo	C57BL/6 mice, MB49 xenograft	reduced tumor size	COX-2; Cyclin D1 ↓	[43]
in vivo	Wistar rats, N-methyl-N-nitrosourea-induced bladder cancer	decreased cell growth, inhibition of invasion	Bcl-2; Survivin ↓ Bax ↑	[55]

Abbreviations: 7-AAD: 7-Aminoactinomycin; ABCC2: ATP-binding cassette sub-family C member 2; Akt: Proteinkinase B; AXL = receptor tyrosine kinase; Bax: Bcl-2-associated X protein; Bcl-2: B-cell lymphoma 2; CD31: Cluster of Differentiation 31; CDK6: cyclin-dependent kinase 6; COX-2: cyclooxygenase-2; CYR61: cysteine-rich, angiogenic inducer, 61; DCK: deoxycytidine kinase; EMT: epithelial mesenchymal transition; ERK: extracellular-regulated kinase; HO-1: heme oxygenase-1; ITGB2: integrin beta 2; JNK: c-Jun N-terminal kinase; KLF5: Krüppel-like factor 5; MMP: Matrix-metalloproteinase; NF-κB: nuclear factor ‘kappa-light-chain-enhancer’ of activated B-cells; PARP: Poly(ADP-ribose)-Polymerase 1; pFAK: phosphorylated focal adhesion kinase; PCNA: proliferating cell nuclear antigen; PGE2: prostaglandin E2; pRb-P: phosphorylated Retinoblastom Protein; ROS: reactive oxygen species; Sp 1/3/4: specificity protein 1/3/4; SRC: Proto-oncogene tyrosine-protein kinase Src; TAZ: transcriptional coactivator with PDZ-binding motif; TIMP-2: tissue inhibitor of metalloproteinases 2; TK: thymidine kinase; TRAIL: tumor necrosis factor-related apoptosis-inducing ligand; Trop-2: tumor-associated calcium signal transducer 2; VEGF: vascular endothelial growth factor; VEGFR1: VEGF receptor 1; YAP: Yes-associated protein; ZO-1: Zonula occludens-1.