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. 2020 Jul 5;12(7):1801. doi: 10.3390/cancers12071801

Table 1.

Profiles of publications concerning CUR selected for the review.

Main Compound [Ref.] Study Goal In Vitro (Cell Line/s)
In Vivo (Model)
Main Conclusions
CUR + 400–550 nm light (1.65 J/cm2) [38] Effect of light on increase in bioavailability and effectiveness of CUR in BC treatment. In vitro: RT112, UMUC3, TCCSUP Photoexcitation of CUR altered migration and adhesion of BC cells by integrin-dependent mechanism (α3, α5 and β1).
CUR (0.1–0.4 μg/mL) + 400–550 nm light (1.65 J/cm2) [39] Effect of light exposure on CUR bioavailability and anticancer efficacy. In vitro: RT112, UMUC3, TCCSUP Inhibition of BC cells by low-dosed CUR exposed to light (0.27 μmol/L) in various cell phases (G0/G1 for cell line RT112, G2/M for TCCSUP, and G2/M- and S-phase for UMUC3) via various molecular action mechanisms.
Vanadyl CUR, vanadyldiacetyl CUR [42] Effect of vanadyl CUR and vanadyldiacetyl CUR on structure, function and antitumor activity of peroxidase enzyme (HRP). In vitro: C5637 Upregulation of horseradish peroxidase (HRP) enzyme stability and activation of peroxidation reaction. Evidence of cytotoxic effect on BC cells.
Gallium CUR, gallium diacetylcurcumin [43] Effect of gallium CUR and gallium diacetylcurcumin on structure, function and antitumor activity of peroxidase enzyme (HRP). In vitro: C5637 Upregulation of horseradish peroxidase (HRP) enzyme stability and activation of peroxidation reaction. Evidence of cytotoxic effect on BC cells.
Lipid-coated polyplex with CUR and anionic plasmid [44] Combination therapy involving hydrophilic genes and hydrophobic drugs for treatment of BC. In vitro: MB49 Development of a lipid carrier system for dual delivery of plasmid DNA and small hydrophobic molecules into MB49 BC cells.
Cyclodextrin–CUR complex (CDC) [45] Effect of CDC complex on human and rat urothelial cancer cells and in AY-F344 orthotopic BC rat model. In vitro: RT4, T24, 253J, RT112
AY-27 (rat cell line),
In vivo: AY-F344 orthotopic BC rat model
Antiproliferative effect (dose-dependent) on rat AY-27 and various cell lines in vitro.
Intravesical instillation of CDC as promising antitumor response.
CUR + melatonin [46] Effectiveness of CUR and melatonin combination therapy by inhibiting proliferation of BC cells. In vitro: T24, UMUC3, 5637
In vivo: Male BALB/c mice
Antiproliferative and antimigration effects of combined CUR and melatonin on BC cells.
Melatonin synergized the ability of CUR to inhibit BC growth, both in vivo and in vitro. The effect of CUR and melatonin on BC cells was related to simultaneous action on cyto c/caspase and IKKβ/NF-κB/COX-2 signaling.
CUR [47] Effect of CUR on human trophoblast cell surface antigen 2 (Trop2) to reduce oncogenic activity of BC cells. In vitro: RT4, RT24 Trop2 as CUR target in RT4 and T24 cell lines.
Inhibition of migration, growth and invasion of cancer cells by CUR can be related to the decreased expression of Trop2 and its downstream target cyclin E1, and the increased level of p27. Apoptosis of BC cells.
CUR [48] Antitumor action mechanisms of CUR in BC. In vitro: T24, 5637 Time- and dose-dependent inhibition of T24 and 5637 cell line proliferation by CUR. Inhibition of epithelial–mesenchymal transition (EMT) and β-catenin signaling pathways.
Resveratrol, CUR [49] Analysis of effects of CUR as potential treatment for reversing drug resistance in BC chemotherapy. In vitro: T24, T24-GCB (gemcitabine-resistant) CUR may reverse the multidrug resistance (MDR) of T24-GCB cells. CUR activates apoptosis by regulation of ABCC2 (increased the expression) and DCK, TK1, TK2 (decreased the expression) as well as increasing PARP cleavage.
CUR and irradiation [50] Possibility of increasing radiation sensitivity in BC. In vitro: T24, HT-1376, SV-HUC-1 Anticancer effect of irradiated CUR due to involvement of miR-1246 in inhibiting p53 gene translation in BC cells.
CUR [51] Effect of CUR on regulation of microRNA-7641 in BC. In vitro: J82, TCCSUP, T24, SV-HUC-1 miR-7641 found to be cancer-stimulating factor. Therapeutic effect of CUR on SV-HUC-1 cells by modulating miR-7641 (downregulation) leading to increased p16 expression being target of miR-7641. CUR revealed proapoptotic effect, which influenced inhibition of proliferation and migration of BC cells.
CUR [52] Preventive action of CUR on cancer stem cells activated by tobacco smoke and role of Wnt/β-catenin pathway in urocystic epithelial–mesenchymal transition. In vitro: T24, SV-HUC-1
In vivo: Male BALB/c mice
Effective reversal by CUR of the activation of Wnt/β-catenin pathway in vitro and in vivo.
CUR [53] Role of CUR in inhibiting growth of BC stem cells and regulation of the Sonic hedgehog (Shh) pathway. In vitro: UM-UC-3, EJ CUR activity against BC stem cells in vitro was observed, especially reducing the cell spheres formation, decreasing expression of cancer stem cells markers, suppressing cell proliferation, and inducing cell apoptosis.
Deactivation of the Shh pathway.
CUR [54] Therapeutic effect of CUR in BC treatment. In vitro: T24, 5637 Time- and dose-dependent cell growth inhibition by CUR. Proapoptotic and antimigration effects of CUR by suppression of matrix metalloproteinase signaling pathways in vitro.
CUR [55] Antitumor action mechanisms in BC treatment. In vitro: T24, UMUC2
In vivo: Female Wistar rats
Anticancer activity of CUR by inhibition of IGF2, suppression of PI3K/AKT/mTOR signaling pathway, and inactivation of N-methyl-N-nitrosourea-induced urothelial tumor tissue.
CUR [56] Preventive effect of CUR on bezidine-induced EMT. In vitro: SV-40 (SV-HUC-1) CUR as promising BC drug due to inhibition of ERK5/AP-1 pathway.
CUR + cisplatin [57] Combination treatment of CUR and cisplatin in BC cells. In vitro: T24, 253J-Bv BC cells apoptosis caused by combination therapy due to reactive oxygen species (ROS) and extracellular regulated kinase (ERK), along with activation of p-MEK and p-ERK1/2.
Apoptosis of 253J-Bv cells caused by increased expression of p53 and p21 proteins.
Apoptosis of T24 cells caused by decreased p-signal transducer and activator of transcription 3(STAT3) expression.
CUR [58] Effect of CUR on proliferation of benzidine-induced BC cells. In vitro: T24 Antiproliferative effect of CUR on benzidine-induced T24 cells through prevention of ERK1/2 activation.
Reduced activation of AP-1 proteins (c-Fos and c-Jun) due to downregulation of ERK 1/2.
CUR [59] Effect of TS on activation of MAPK pathway and EMT changes in BC and preventive effect of CUR. In vivo: Male BALB/c mice CUR-induced inhibition of activation of ERK1/2, JNK and p38 MAPK pathways, and AP-1 proteins. Prevention of epithelial-mesenchymal transition (EMT) in the BC.
CUR (160 μmol/L) [60] Use of CUR in BC treatment. In vitro: SPF-grade Wistar rats + N-methyl-N-nitrosourea Proapoptotic effect of CUR by stopping G1/S phases of cell cycle and increasing Bax protein expression.
CUR (5 and 15 μM) + 5-fluorouracil (5-FU) [61] Effect of CUR on 5-FU toxicity in BC cells In vitro: EJ138 5-FU cytotoxicity was dependent on CUR concentration.
BDMC with α-PD-L1 antibody [62] Combination treatment of BDMC and α-PD-L1 antibody on survival of BC cells. In vivo: Female C57BL/6 mice with MB49 mouse BC cells BDMC with α-PD-L1 antibody appeared as promising therapy against BC. BDMC enhanced CD8+ T cell response, elevated the level of IFN-γ in the blood, and suppressed myeloid-derived suppressor cells due to combination treatment.
Theracurmin® (nanocurcumin), CUR [63] Anticancer effect of Theracurmin® and CUR compounds on BC cells. In vitro: T24R2, 253J, HTB9 Comparable efficacy of Theracurmin® and CUR. Dosage and time-dependent antitumor effect of Theracurmin® due to activation of apoptosis and arresting the cell cycle in sub-G1, and dysregulation of S and/or G2/M phases.