Table 3.

In vitro evidence of the effects of curcumin on androgen-sensitive prostate cancer cells.

Cell Line	Curcumin Dosage	Effects	Reference
LNCaP	0–50 μM; 72 h to assess cell proliferation and cell morphology 20 μM; 24 h to assess expression of Bcl-2, Bcl-xL and Bax 0–50 μM; 24 h to assess PARP cleavage, AR expression, and PSA levels.	↓ Proliferation ↑ Lifted, round cells ↓ Bcl-2 protein ↓ Bcl-xL protein ↑ Phosphatidylserine translocation to outer plasma membrane ↑ PARP cleavage ↓ AR protein ↓ PSA secretion	[54]
LNCaP	10 and 50 μM; 1–4 days to assess cell viability 0–100 μM; 5 h to assess NF-κB expression 50 μM; 0–72 h to assess the expression of Bcl-2 and Bcl-xL 100 μM; 0–72 h to assess the expression and activity of procaspases 3 and 8 50 μM; 0–4 days to assess cell proliferation, PARP cleavage, and apoptosis	↓ Cell viability ↓ Proliferation ↓ NF-κB protein activation ↓ Bcl-2 protein ↓ Bcl- xL protein ↑ Procaspase-3 and -8 activity ↑ PARP cleavage ↑ Apoptosis	[55]
LNCaP	40 μM; 21 days to assess colony formation efficiency 0–50 μM; 24 h to assess cell growth 40 μM; 24 h	↓ Cell growth ↓ AR ↓ AR transcriptional activity ↓ AR transactivation ↓ c-Jun ↓ AP-1 ↓ CBP ↓ Colony formation efficiency	[56]
LNCaP	0–100 μM; 24 h to assess cell proliferation and cyclin D1 protein expression 0–50 μM; 24 h to assess DNA synthesis 25 and 50 μM; 3 and 24 h to assess cell viability 50 μM; 0–180 min and 30–120 min to assess cyclin D1 mRNA expression and CDK4 activity 10 μM; 0–120 min to assess Cyclin D1 promoter activity	↓ Proliferation ↓ DNA synthesis ↓ Cyclin D1 protein and mRNA ↓ CDK4 activity ↓ Cyclin D1 promoter activity	[57]
LNCaP	5–40 μM; 48 h to assess cell viability, caspase activity, DNA fragmentation 10 μM; 20 h to assess cytochrome c release and protein expression of procaspases	↓ Cell viability ↑ TRAIL sensitivity ↑ Cell-cycle arrest at the G2/M phase ↓ Bid protein ↓ Mitochondrial cytochrome c	[58]
LNCaP	35 μM; 0–4 h	↓ p-Akt	[59]
C4-2B	0-15 μM; 1 h to assess EGFR autophosphorylation 1–10 μM; 1 h to assess CSF-1 phosphorylation 7.5 μM and 15 μM; 12 days to assess cell mineralization, IKK activity, and COX-2 expression	↓ EGFR autophosphorylation ↓ CSF-1 phosphorylation ↓ Cell mineralization ↓ IKK activity ↓ COX-2 protein	[48]
LNCaP	10 μM; 48 h to assess cytotoxicity 10 μM; 20 h to assess cleavage of procaspase-3 12.5–50 μM; 20 h to assess NF-κB expression 12.5 μM; 4 and 20h to assess IκBα expression	↑ Cytotoxicity ↑ Apoptosis ↓ NF-κB ↓ P-IκBα ↑ Cleaved caspase-3	[60]
LNCaP	0–40 μM; 24 h	↓ NKX3.1 mRNA and protein ↓ AR mRNA and protein ↓ ARE binding activity	[69]
LNCaP	0–50 μM; 0–72 h	↓ MDM2	[70]
LNCaP	0–30 μM; 48 h to assess cell viability and the expression of Bcl-2, Bax, and Bak 0–30 μM; 3 weeks to assess colony formation efficiency 0–30 μM; 24 h to assess caspase-3 activation and PARP cleavage 0–20 μM; 6–24 h to assess the expression of Bim, Bax, Bak, PMMA, Noxa, Bcl-2, and Bcl-xL genes, and p110, p85, and p-Akt proteins 0–30 μM; 0–24 h to assess mitochondrial membrane potential, release of mitochondrial proteins, translocation of Bax and p53 to the mitochondria, and p53 acetylation and phosphorylation	↓ Cell viability ↓ Colony formation ↑ Caspase-3 activation and nuclear translocation ↑ PARP cleavage ↓ Bcl-2 protein and mRNA ↑ Bax protein and mRNA ↑ Bak protein and mRNA ↑ Bim mRNA ↑ PΜMA mRNA ↑ Noxa mRNA ↓ Bcl-xL mRNA ↓ Mitochondrial membrane potential ↑ Release of Smac/ DIABLO, cytochrome c, and Omi/HtrA2 proteins from mitochondria ↑ Translocation of Bax and p53 to the mitochondria ↑ p53 acetylation and phosphorylation ↑ ROS ↓ p110 ↓ p85 ↓ p-Akt	[61]
LNCaP	10 μM; 48 h to assess cell viability and NF-κB expression 10–30 μM; 24 h to assess Akt phosphorylation 10–30 μM; 24 h to assess protein expression	↓ p-Akt	[71]
LNCaP	25 μM; 17 h	↑ MKP5 mRNA	[72]
LNCaP	0–30 μM; 24 h to assess cell viability 5–40 μM; 21 days to assess colony formation efficiency and TRAIL-induced apoptosis 0–10 μM; 24 h to assess expression of DR4, DR5, DcR1, and DcR2 0–20 μM; 24 and 48 h to assess the expression of pro- and antiapoptotic proteins, caspases, cleaved PARP, and mitochondrial membrane potential	↓ Cell viability ↓ Colony formation efficiency ↑ TRAIL-induced apoptosis ↑ DR4 death receptor ↑ DR5 death receptor ↑ Bak ↑ Bax ↑ PMMA ↑ Bim ↑ Noxa ↓ Bcl-2 ↓ Bcl-xL ↑ Bid cleavage to tBid ↓ IAPs ↓ XIAP ↓ Mitochondria membrane potential ↑ Caspase-3, -8, and -9 cleavage ↑ PARP cleavage	[62]
LNCaP	20 μM; 24 h to assess cell-cycle progression 0–20 μM; 48 h and 20 μM; 0-48 h to assess apoptotic processes 0–20 μM; 0–48 h to assess protein expression	↑ Cell cycle arrest at the G1/S phase ↑ Apoptosis ↑ p27 ↑ p21 ↓ Cyclin D1 ↓ Cyclin E	[63]
LNCaP, C4-2B	0–100 μM; 24–74 h to assess cell proliferation 10 μM; 3–48 h to assess gene expression 5–20 μM; 12 h to assess protein and gene expression, and PSA ELISA	↓ Proliferation ↓ Cell growth ↑ Methionine tRNA synthase ↑ Hemeoxygenase decyclizing ↑ Transcription corepressor activity ↓ Kallikrein 2, 3 ↓ NEDD4- binding protein ↓Transmembrane proteases ↓ Cyclin B1 ↓ AR protein ↓ NKX3.1 ↓ PSA ↓ ERBB2 ↓ EGFR	[73]
LNCaP	0–80 μM; 24–72 h to assess cell proliferation 0–20 μM; 24 h	↓ Proliferation ↓ PSA protein and mRNA ↓ AR mRNA ↓ IL-6	[74]
LNCaP	10 μM, 25 μM, or 50 μM; 24 h	↓ Cell viability ↑ Apoptosis ↓ Necrosis	[75]
TRAMP-C2	0–100 μM; 24 and 72 h	↓ Cell growth ↓ Gli1 (Hedgehog signaling)	[76]
LNCaP	25, 50, and 100 μM; 24–72 h to assess apoptosis and DNA fragmentation	↑ Apoptosis ↑ Ceramide ↑ ssDNA	[66]
LNCaP	0–100 μM; 24 and 48 h to assess cell proliferation 0–30 μM; 24 h to assess AR expression 25 μM; 24 h to assess expression of proteins in the Wnt/β-catenin signaling pathway	↓ Proliferation ↓ AR↓ Nuclear β-catenin ↓ GSK-3b ↓ c-myc ↓ Wnt/β-catenin pathway	[64]
22RV1, LNCaP	10–100 μM; 4 and 24 h 20 μM; 24 h in 22RV1 and DU-145 only for fluorescent microscopy and nuclear staining	↑ Curcumin compartmentalization within cytoplasm and exclusion from nucleus ↑ Cytotoxicity ↑ Apoptosis ↑ Autophagy ↑ LC3B-II isoform ↑ Cell-cycle arrest at the G2 stage ↓ Cyclin B1 ↓ PCNA ↓ β-catenin signaling ↓ c-myc mRNA ↓ Survivin mRNA ↓ Cyclin D1 mRNA ↓ TCF-4 ↓ CREB binding protein ↓ P300	[77]
LNCaP	10 μM; 24 h	↓ AR ↓ PSA	[78]
TRAMP-C1	2.5 and 5 μM; 5 days to assess protein and gene expression 5–100 μM; 1 h to assess methylation	↓ Hypermethylation of CpG sites in Nrf2 ↑ Nrf2 ↑ NQO-1 ↓ CpG methylase (M.Sssl) activity	[79]
LNCaP	5 μM; 7 days	↑ Cytotoxicity ↓ Tri-methylation of H3K27 (H3K27me3) ↓ Methylation of Neurog1 gene ↑ Neurog1 ↑ HDAC1 ↑ HDAC4 ↑ HDAC5 ↑ HDAC8 ↓ HDAC3 ↓ HDAC activity	[80]
LNCaP, 22RV1	20 μM; 24 h 0–50 μM; 24 to assess AR expression	↓ AR ↑ HSP90AA1, GJA1, PRKCE, XRCC6, MIR-141, MIR-183, HMGB1	[81]
LNCaP, C4-2B	5–40 μM; 48 h to assess cell proliferation 20 μM; 24 h for immunoblotting and PCR 15 μM; 1 h for aggregation assay 5 and 10 μM; 24 h for Boyden’s chamber assay	↓ Proliferation ↓ β-catenin signaling ↓ Nuclear β-catenin ↑ β-catenin localization in membrane ↑ Cell–cell aggregation ↑ P-PKD1 ↑ Inactive p-cofilin	[82]
LNCaP, CW22RV1, C-33	0–50 μM; 16 h 25 and 50 μM; 30 min acute treatments	↓ Cell migration/invasion ↓ Total and activated matripase	[83]
LNCaP	25 μM; 48 h to evaluate apoptosis, gene and protein expression 25 μM; 24 h to assess H2O2 production 1.6–25 μM; 48 h to assess cell viability 10–50 μM; 30 min to assess ROS production	↓ Cell viability ↑ Cytotoxicity ↑ Apoptosis ↓ Bcl-2 ↑ Bax ↑ ROS ↑ CuZnSOD ↑ TRX1 oxidation ↑ TRXR1 mRNA	[84]
LNCaP, 22RV1	0–50 μM; 0–72 h to assess cell proliferation 0–50 μM; 6 h for apoptosis assay 0–50 μM; 24h to assess protein expression and levels of DHT	↓ Cell viability ↑ Caspase-3/7 ↓ DHT ↑ AKR1C2 ↑ SRD5A1 ↓ StAR ↓ CYP11A1 ↓ HSD3B2	[85]
LNCaP	10 U/mL 74 h to assess cell viability	↑ Apoptosis ↓ p-JNK ↓ c-Jun ↓ Bcl-2 mRNA ↓ Tertiary methylation of H3K4	[86]
LNCaP, C4-2B	10 μM; 3–48 h to assess gene expression	↑ Apoptosis ↑ Cell-cycle arrest ↓ Myc ↑ Heme Oxygenase-1 ↑ Cyclic AMP-dependent transcription factor ↓ RAF1 ↓ RAF1 ↓ IGF1R ↓ BCL6 ↑ PTEN ↑ EGFR1 ↑ SMAD ↑ FOXO3 ↑ Akt1 ↑ RAD51 ↓ SOX4 ↓ EGFR ↓ WT1 ↓ E2F2 ↓ MALAT1↑ BMP receptor signaling ↑ PTEN-regulated cell-cycle arrest ↓ TGF-b receptor signaling ↓ WNT signaling ↓ AP-1 ↓ NF-κB signaling ↓ PI3K/Akt/mTOR signaling ↓ FOXM1 ↑ IL-6 signaling ↑ FTH1 ↑ CPEB4 ↑ C6orf61 ↓ PMEPA1	[87]