Table 1.
The mechanisms of curcumin on cancers.
| Study Type | Models | Dose & Duration | Effects | Mechanisms | Ref. |
|---|---|---|---|---|---|
| Breast cancer | |||||
| In vitro In vivo | MDA-MB-231 and MDA-MB-468 cells; female BALB/c-nu/nu mice with MDA-MB-231 adherent cells | 10, 15, 20, 25, 30 and 35 µM, 24, 48 and 72 h | Inhibiting proliferation, invasion and migration, EMT and stemness | ↓PTCH1, SMO, Gli1, Gli2, N-cadherin, vimentin, Oct4, Sox2 | [27] |
| In vitro | MCF-7 and MDA-MB-231 cells | 6.25, 25 and 100 µM, 24 h | Cytotoxicity and photosensitizing effect | ↓PTP1B; ↑ROS |
[28] |
| In vitro | MCF-7/TAMR cells | 5, 10, 20, 30 and 40 µM, 48 h | Preventing cell migration and invasion, and EMT | ↓N-cadherin, H19; ↑E-cadherin |
[29] |
| In vitro | MCF-7 and MDA-MB-231 cells | 5, 10, 20, 40, 60, 80, 100, 120 and140 μM, 24 and 48 h | Inhibiting cell viability; Promoting oxidative stress, ER stress, and ferroptosis |
↑HO-1, Nrf2, ROS, HSPA5, ATF4, DDIT3, MDA, FTL, TFRC, FTH1, BACH1, RELA, USF1, NFE2L2; ↓GPX4, GSH |
[30] |
| In vitro In vivo | MDA-MB-231 cell; BALB/ c nude mice with MDA-MB-231 cells |
5, 10, 20 and 50 μM, 24 h; 25 g/kg, 4 weeks | Inhibiting cell proliferation and cancer growth | ↑GFPu, miR-142-3p; ↓PSMB5, PSMB1, P300, CT-1 |
[31] |
| In vitro, In vivo | MCF-7, MDA-MB-231 and MDA-MB-468 cells; female BALB/c nude mice with MDA-MB-231 cells | 20 and 40 µM, 48 h; 100 mg/kg/2 days, 21 days | Inhibiting proliferation, migration and invasion; Promoting apoptosis; Blocking the cell cycle |
↓cyclin A1, CDK1, Bcl-2, EZH2; ↑Caspase-9, DLC1 |
[32] |
| In vitro | MCF-7 and MDA-MB-231 cells | 10, 15, 20, 25, 30, 35 and 40 µM, 24 and 48 h | Inhibiting cell viability, invasion and migration, mammosphere formation and differentiation abilities, stem cell properties | ↓CD44+CD24− subpopulation, vimentin, fibronectin, β-catenin, Oct4, Nanog, Sox2; ↑E-cadherin |
[33] |
| In vitro | HCC-38, UACC-3199, and T47D cells | 5 and 10 µM, 3 days | Suppressing proliferation and methylation | ↓DNMT1, miR-29b, SNCG; ↑BRCA1, TET1, DNMT3 |
[34] |
| In vitro | MCF-7 and MDA-MB-231 cells | 5, 10 and 25 µM, 48 h | Inhibiting cell vitality; Inducing apoptosis |
↓TLR4, TRIF, IRF3, IFN-α/β | [35] |
| In vitro | MCF-7, MDA-MB-453 and MDA-MB-231 cells | 5, 10, 15, 20, 25 and 30 µM, 24, 48 and 72 h | Inhibiting proliferation, invasion and metastasis; Inducing apoptotic cell death and cell cycle arrest |
↓Src, pSTAT-1, p-Akt, p-p44/42, Ras, c-raf, vimentin, β-catenin, p53, Rb, p-Rb, Bax, Bcl-2, Bcl-xL, Mcl-1; ↑PIAS-3, SOCS-1, SOCS-3, ROS, NF-κB, PAO, SSAT, p21, Bak |
[36] |
| In vitro | T47D, MCF7, MDA-MB-415, SK-BR-3, MDA-MB-231, MDA-MB-468 and BT-20 cells | 10 and 30 µM, 24 and 48 h | Inhibiting proliferation; Inducing G2/M arrest and apoptosis |
↓CDC25, CDC2, p-Akt, p-mTOR, p-S6, Bcl-2; ↑p21, Bax, Cleaved-caspase-3 |
[37] |
| In vitro | MDA-MB-231 and CAL-51 cells | 5 µM, 48 h | Inhibiting proliferation; Inducing apoptosis |
↓Bcl-2, RAD51; ↑ROS, Bax, γH2AX |
[24] |
| Lung cancer | |||||
| In vitro In vivo | H1650, H1299, H460 and A549 cells; BALB/c nude mice with A549 cells | 10, 20 and 40 μM, 24 h; 50 mg/kg, 22 days | Accelerating apoptosis; Inhibiting migration, invasion and xenograft tumor growth |
↓circ-PRKCA, ITGB1; ↑miR-384 |
[38] |
| In vitro In vivo | H460, H1299, H1975, A549, SCC-827, PC-9 and CMT-64 cells; female C57bl/6j mice with CMT-64 cells | 4, 8, 12, 16, 20, 24 and 28 μg/mL, 24 h; 5 mg/kg, 24 h | Inhibiting of tumor growth and volume; Ameliorating the immunosuppressive micro-environment |
↓MDSCs cells, Treg cells, IL-10; ↑NK cells |
[39] |
| In vitro | H1299 and A549 cells | 2.5, 5 and 7.5 μM, 48 h | Decreasing migration, invasion and EMT Process | ↑TAp63α, E-cadherin, ZO-1; ↓Vimentin, N-cadherin, miR-19a, miR-19b |
[40] |
| In vitro In vivo | A549 and H1299 cells; female C57BL/6 mice with Lewis lung carcinomas cells | 5, 10, 20, 30 and 40 μM, 24 h; 100 mg/kg/day, 15days | Inhibiting tumor growth; Inducing ferroptosis and autophagy |
↓SOD, GSH, SLC7A11, GPX4, p62; ↑MDA, iron, ACSL4, Beclin1, LC3-II, autolysosome, mitochondrial damage |
[41] |
| In vitro In vivo | A549/GR and H520/GR cells; BALB/c nude mice with A549/GR cells | 50, 100 and 150 μM, 48 h; 100 mg/kg, 3 weeks | Suppressing proliferation; Promoting apoptosis |
↑lncRNA-MEG3, PTEN | [42] |
| In vitro | A549, NCI-H1299 | 5, 25, 125 and 250 nM, 24, 48 and 72 h | Suppressing sphere size and number, and stemness | ↓ALDH, CD133, Epcam, Oct4, TAZ; ↑Hippo pathway, p-TAZ |
[43] |
| In vitro | H446 cells | 5, 10, 15 and 20 μM, 24 and 48 h | Inducing cell apoptosis; Regulating cell cycle |
↓Bcl-2, CCNF, LOX1, MRGPRF, and VEGFB; ↑Bax, cytochrome-C, miR-548ah-5p |
[44] |
| In vitro | A549 cells | 1, 2, 5, 10 and 20 μM, 24 and 48 h | Inhibiting migration and invasion | ↓E-cadherin, sE-cad, vimentin, slug; ↑N-cadherin, snail, MMP-9 |
[45] |
| In vitro | A549 cells | 25, 50 and 100 μM, 48 h | Inhibiting proliferation; Inducing apoptosis |
↓14-3-3 proteins, p-Bad, p-AKT/AKT, Caspase-9, PARP; ↑Cleaved-caspase-9, Cleaved-PARP |
[46] |
| In vitro | A549 cells | 5, 10, 20 and 40 μM, 24, 48, 72 and 96 h | Inhibiting proliferation; Inducing apoptosis and autophagy |
↓p-Akt, p-mTOR, p62, LC3-I; ↑Beclin1, LC3-II |
[47] |
| In vitro | A549 cells | 10, 20 and 40 μM, 12, 24 and 48 h | Inhibiting migration and invasion | ↓miR-25-5p; ↑miR-330-5p |
[48] |
| In vitro | A549 and H1299 cells | 0.5, 1, 5, 10 and 20 µM, 24, 48 and 72 h | Inhibiting colony formation; Promoting apoptosis and autophagy |
↓p-mTOR, p-S6, p-PI3K, p-Akt ↑LC3-II/ LC3-I, Beclin-1 |
|
| Colorectal cancer | |||||
| In vitro In vivo | TCO1 and TCO2 cells; SCID mice with organoid cells | 0.6, 2, 6 and 20 µg/mL, 72 h; 20 mg/day, 21 days | Inducing necrotic lesions and apoptosis; Inhibiting stemness and proliferation |
↓cyclin D1, c-MYC, p-ERK, CD44, CD133, LGR5 | [49] |
| In vitro In vivo | CC531 cells; tumor-bearing rats with CC531 cells | 15, 20, 25 and 30 µM, 24, 48 and 72 h; 200 mg/kg/day, 28 days | Reducing proliferation and migration; Diminishing global tumor progression |
↑AST, ALP, albumin; ↓cholinesterase, cholesterol, and total protein |
[50] |
| In vitro | SW620 cells | 1, 5 and 25 μM, 48 h | Inhibiting tumor sphere formation; Inducing apoptosis and autophagy |
↓GP1BB, COL9A3, COMP, AGRN, ITGB4, LAMA5, COL2A1, ITGB6, LGR5, TFAP2A, ECM; ↑Autolysosomes, autophagosomes |
[51] |
| In vitro In vivo | SW480 and HT-29 cells; BALB/c nude mice with SW480 cells | 10, 20, 30, 40, 50 and 60 µM, 24 h; 100 mg/kg/day, 3 weeks | Inhibiting proliferation and tumor volume and weight; Inducing apoptosis |
↓NNMT, p-STAT3, G2/M phase cell cycle arrest; ↑ROS |
[52] |
| In vitro | HCT-116/L-OHP cells | 10, 20, 30 and 40 µM, 48 h | Inhibiting proliferation, migration and invasion; Arresting cell cycle distribution |
↓ERCC1, Bcl-2, GST-π, MRP, P-gp; ↑miR-409-3p |
[53] |
| In vitro | 5-FU resistant HCT-116 cells | 5, 10, 20 and 40 μM, 48 h | Inhibiting proliferation; Inducing apoptosis; Blocking G0/G1 phase |
↓E-cadherin, β-catenin, TCF4, Axin; ↑TET1, NKD2, vimentin |
[54] |
| In vitro | SW480 cells | 0.1, 0.2 and 0.4 µM, 24 h | Inhibiting EMT and the expression of DNMTs | ↑E-cadherin; ↓N-cadherin, twist, snail, vimentin, CDX2, DNMT1, DNMT3a, Wnt3a, β-catenin |
[55] |
| In vitro In vivo | HCT8 and HCT8/DDP cells; Nude mice with HCT8/DDP cells | 10 μM, 48 h; 1 g/kg/week, 42 days | Reducing tumor volume and weight; Promoting apoptosis |
↓Bcl-2, KCNQ1OT1; ↑cytochrome C, Bax, Cleaved-caspase-3, Cleaved-PARP1, miR-497 |
[56] |
| In vitro | HCT116, HCT8, SW480 and SW620 cells | 10 μM, 24 h | Reducing clone formation | ↑NBR2, p-AMPK, p-ACC; ↓p-S6K/p-S6, Mtor, S-phase |
[57] |
| In vitro | SW480 and 5FU-SW480 cells | 5, 10, 15, 20, 25, 30, and 50 μM, 48 and 72 h | Inducing apoptosis; Decreasing colony formation and migration |
↓insulin, IGF-1 receptors | [58] |
| In vitro, In vivo | HCT116/OXA and HCT116 cells; BALB/c nude mice with HCT116/OXA cells | 1, 2, 4, 8, 16, 32 and 64 μM, 48 h; 60 mg/kg, 3 weeks | Inhibiting tumor volumes and weights; Decreasing the migratory ability |
↓p-p65, Bcl-2, p-Smad2, p-Smad3, N-cadherin, TGF-β; ↑Cleaved-caspase3, E-cadherin |
[59] |
| In vitro | HT-29 and DLD-1 cells | 15, 20 and 25 μM, 48 h | Inducing apoptosis and G2/M cell cycle arrest | ↓p-Akt, p-Bad, Bcl-2, GPX1, GPX4; ↑ROS, HSP27, Bad, cPARP, Beclin 1, p62 |
[60] |
| In vitro In vivo | SW480 cells; female nude mice with SW480 cells | 40 μM, 24 h; 200 mg/kg, 5 days | Suppressing proliferation | ↓β-catenin, TCF4, miR-21, miR-130a; ↑Nkd2 |
[61] |
| In vitro | HCT-116 and HCT-8 cells | 2.5, 5, 10, 20 and 40 µM, 24 h | Inhibiting proliferation, migration and stem-cell like characteristics | ↑CD44 | [62] |
| Head and Neck Cancer | |||||
| In vitro In vivo | HNSCC cell lines SNU1076, SNU1041, FaDu and SCC15; C57BL/6 mice with SCC15 cells | 1, 2, 5, 10, 20, 40 and 80 µM, 1, 3, 6, 12 and 24 h; 50 mg/kg, 6 weeks | Inhibiting cell viability, invasion, EMT, and tumor formation and growth; Enhancing ability of effector T cells to kill cancer cells and immune response to tumors |
↓p-STAT3, TIM-3+CD4+ T cells, PD-1+CD8+ T cells, TIM-3+CD8+ T cells, CD4+CD25+FoxP3+ Treg cells, PD-1, TIM-3; ↑E-cadherin, CD8+ T cells, IFN-γ |
[63] |
| In vitro | SCC-9, FaDu and HaCaT cells | 50, 25, 10, 5, 2.5, 1.25 and 0.75 μM, 24 and 48 h | Reducing cell viability; Inducing cell cycle arrest; Modifying cytoskeleton organization |
↓procaspase-3, EGFR, PLD1, RPS6KA1, p-mTOR, p-AKT, PI3K; ↑Caspase-3, PRKCG, EGF |
[64] |
| Gastric cancer | |||||
| In vitro | AGS cells | 10, 20, 30, 40, 50, 60, 70, 80, 90 and 100 µM, 24, 48 and 72 h; 50 mg/kg, 6weeks | Inducing apoptosis; Suppressing proliferation |
↓Bcl-2, survivin; ↑Bax, the proportion of Sub-G1 cells |
[65] |
| In vitro | MGC-803 cells | 5, 10, 15, 20, 40 and 60 μM, 24, 48 and 72 h | Inhibiting proliferation and migration; Promoting mitochondrial and DNA damage, and apoptosis |
↓Δ ψm, cyclin E1, DNMT1, p-Rb, methylated CpG sites; ↑ROS, ATM, ATR, GADD45A, p21, p-p53, p-γH2AX |
[66] |
| In vitro | SGC-7901 cells | 10, 20, 40 and 80 µM, 48 h | Suppressing proliferation, invasion, and cytoskeletal remodeling ability; Inducing apoptosis |
↓Gli1, Foxm1, β-catenin, pseudopods, skeleton fibers, vimentin; ↑S stage, E-cadherin |
[67] |
| In vitro In vivo | SGC-7901 cells; BALB/c male nude mice with SGC-7901 cells | 50 μM, 24, 48 and 96 h | Decreasing migration, invasion and growth of transplanted tumors; Promoting cell apoptosis |
↓Bcl-2, cyclin D1, CDK4; ↑miR-34a |
[68] |
| In vitro | SGC-7901 and BGC-823 cells | 10, 20 and 40 μM, 24 h | Inhibiting proliferation; Promoting apoptosis and autophagy |
↓Bcl-2, Bcl-xL, LC3I, PI3K, p-Akt, p-mTOR; ↑Bax, Beclin1, ATG3, Cleaved-caspase-3, Cleaved-PARP, ATG5, LC3II, p53, p21 |
[69] |
| In vitro In vivo | SGC-7901 cells; Balc/c nude mice with SGC7901 cells | 25 μM, 3, 5 and 7 days; 100 mg/kg, 2 weeks | Inhibiting proliferation, gastrin and gastric acid secretion; Promoting apoptosis |
↑Caspase-3 | [70] |
| Bladder cancer | |||||
| In vitro | T24 and RT4 cells | 10, 15, 20 and 25 µM, 48 and 72 h | Inhibiting cell growth, migration and invasion; Inducing cell cycle arrest |
↓Trop2, cyclin E1; ↑G2/M cell populations, p27 |
[71] |
| In vitro | J82, TCCSUP and T24 cells | 1, 5, 10 and 20 µM, 24, 48 and 72 h | Decreasing invasion and tumorigenicity; Increasing apoptosis |
↓miR-7641; ↑p16 |
[72] |
| Prostate Cancer | |||||
| In vitro | PC-3 and DU145 cells | 10, 20, 30, 40 and 50 µM, 12, 24 and 48 h | Reducing cell viability, migration and invasion; Promoting apoptosis |
↓PCLAF, Bcl-2, Caspase-3; ↑miR-30a-5p, Bax, Cleaved-caspase-3 |
[73] |
| In vitro | Prostate-CAFs, PC-3 and NAFs cells | 10, 20 and 30 μM, 8, 12 and 24 h | Inducing apoptosis and ER stress; Regulating cell cycle |
↓Bcl-2, ΔΨm; ↑Cleaved-caspase-3, Bax, Bims, Cleaved-PARP, Puma, p-p53, ROS, p-ERK, p-eIF2α, CHOP, ATF4 |
[74] |
| In vitro In vivo | LNCaP and 22Rv1 cells; male TRAMP mice | 5, 25 and 50 μM, 24, 48 and 72 h; 200 mg/kg/day, 30days | Inhibiting growth; Inducing apoptosis |
↓CYP11A1, HSD3B2, StAR, testosterone, dihydrotestosterone; ↑AKR1C2, SRD5A1, CYP17A1 |
[75] |
| In vitro | 22RV1, PC-3 and DU145 cells | 1, 5, 10 and 20 μM, 4 days | Suppressing proliferation | ↓cyclin D1, PCNA, β-catenin, c-MYC; ↑p21, miR-34a |
[76] |
| Thyroid cancer | |||||
| In vitro | K1, FTC-133, BCPAP and 8505C cells | 10, 12.5, 20, 25, 30, 40 and 50 µM, 24 and 72 h | Inhibiting cell growth; Inducing autophagy |
↑LC3-II, Beclin-1, p-p38, p-JNK, p-ERK1/2; ↓p62, p-PDK1, p-Akt, p-p70S6, p-p85S6, p-S6, p-4E-BP1 |
[77] |
| In vitro | TPC-1 and BCPAP-R cells | 2.5, 5, 10, 20 and 40 µM, 24 h | Inhibiting cell viability, invasion, migration and EMT | ↓MMP-9, MMP-2, N-cadherin, vimentin, fibronectin, p-JAK, p-JAK2, p-JAK3, p-STAT1, p-STAT2; ↑E-cadherin, miR-301a-3p |
[78] |
| Liver cancer | |||||
| In vitro In vivo | HepG2, Huh-7 and MHCC-97H cells; BALB/c-nu nude mice with HepG2 cells | 1.2, 2.4, 4.8 and 9.6 µg/mL, 24 and 48 h; 120 and 240 mg/kg/day, 15 days | Reducing tumor volume and weight, and angiogenesis | ↓MDSCs, GM-CSF, G-CSF, TLR4, MyD88, p-IKKα, p-IKKβ, NF-κB, TNF-α, IL-6, IL-1β, PGE2, COX-2, VEGF, CD31, α-smooth | [79] |
| In vitro | HepG2 and HuT78 cells | 5 and 10 μM, 24 h | Inducing cell death | ↓lactate, ldh-a, mct-1, mdr-1, stat-3, HIF-1α, HCAR-1; ↑NO |
[80] |
| In vitro | HepG2 cells | 20, 50, 80 and 100 μM, 24, 48 and 72 h | Inhibiting proliferation, migration and invasion; Promoting apoptosis |
↓HSP70, eHSP70, TLR4 | [25] |
| In vitro In vivo | Bel-7,402 and HepG2 cells; male BALB/c mice with H22 cells | 15 and 30 μM, 24, 48 and 72 h; 100 mg/kg/day, 14 days | Inducing apoptosis, G2/M cell cycle arrest; Modulating gut microbiota |
↓p-PI3K, p-Akt, p-mTOR, tumors weights and sizes; ↑Cleaved-caspase-3, Lactobacillus, Epsilonbacteraeota, Helicobacterac-eae, Campylobacterales, Helicobacter, Escherichia-shigella, Bifidobacterium, Campylobacteria |
[81] |
| In vitro In vivo | HepG2 and SK-HEP1 cells; male BALB/c mice H22 and HepG2 cells | 20, 40, 60, 80, 100, 120 and 140 nM, 24 h; 100 mg/kg curcumin or Zn (II)-curcumin, 2 weeks | Inhibiting tumor growth; Regulating gut microbiota; Improving intestinal permeability |
↓Firmicutes, unclassified Lachnospiraceae, Clostridium cluster XIVa, Pseudoflavonifractor, Oscillibacter; ↑Bacteroidetes, Barnesiella, Unclassified_Porphyromonadaceae, Paraprevotella, Prevotella, zonula occludens-1, occludin |
[82] |
| Ovarian cancer | |||||
| In vitro | SKOV3 cells | 10, 20, 30, 40 and 50 μM, 6, 12 and 24 h | Inhibiting migration and invasion | ↓STAT3, fascin | [83] |
| In vitro | SKOV3 cells | 20 μM, 96 h | Inhibiting cell migration and EMT | ↓DNMT3a, β-catenin, cyclin D1, c-Myc, fibronectin, vimentin; ↑SFRP5, E-cadherin |
[84] |
| In vitro | SK-OV-3 and A2780 cells | 5, 10, 20, 40 and 80 μM, 24, 48 and 72 h | Inducing apoptosis and autophagy | ↓p62, p-AKT, p-mTOR, p-p70S6K; ↑Caspase-9, PARP, Atg3, Beclin-1, LC3B-I/II |
[85] |
| In vitro In vivo | SKOV3 and A2780 cells; BALB/c athymic mice with A2780 cells | 10, 20 and 40 μM, 24, 48 and 72 h; 15 mg/kg/2days, 5 weeks | Inhibiting proliferation; Promoting apoptosis |
↓PCNA, miR-320a; ↑Bax, Cleaved-caspase-3, circ-PLEKHM3, SMG1 |
[86] |
| Oral Cancer | |||||
| In vitro | HSC-4 and Ca9-22 cells | 15 μM, 48 h | Decreasing invasion, migration and EMT | ↓vimentin, p-c-Met, p- ERK, pro-MMP9; ↑E-cadherin |
[87] |
| Pancreatic Cancer | |||||
| In vitro | Panc-1 and MiaPaCa-2 cells | 6, 10 and 12 µM, 24 h | Reducing cell survival; Inducing apoptosis and DNA damage |
↓G0/G1-fraction; ↑yH2AX-MFI, G2/M-fraction, S-phase cells |
[88] |
| In vitro | PANC-1 cells | 2.5, 5, 10 and 20 µM, 72 h | Inducing apoptosis | ↑Cleaved-caspase-3, miR-340, Cleaved-PARP; ↓PARP, XIAP |
[89] |
| In vitro | Patu8988 and Panc-1 cells | 5, 10, 15 and 20 μM, 48 and 72 h | Inhibiting migration and invasion; Inducing apoptosis |
↓NEDD4, p-Akt, p-mTOR; ↑PTEN, p73, β-TRCP |
[90] |
| Cervical Cancer | |||||
| In vitro | Siha cells | 5, 15, 30 and 50 µM, 6, 12, 24 and 48 h | Inhibiting proliferation; Inducing G2/M cell cycle arrest, apoptosis, autophagy |
↓cyclins B1, cdc25; ↑ROS, p62, LC3I/II, Cleaved-caspase-3, Cleaved-PARP, p53, p21 |
[91] |
| In vitro | Siha cells | 20 µM, 72 h | Decreasing EMT and migration | ↓N-cadherin, vimentin, slug, Zeb1, PIR, pirin; ↑E-cadherin |
[92] |
| Tongue Cancer | |||||
| In vitro | CAL 27 cells | 10, 25, 50 and 100 µM, 16 and 24 h | Inhibiting proliferation and migration; Promoting apoptosis and S-phase cell cycle arrest |
↓Bcl-2; ↑Bax, Cleaved-caspase-3, S-phase cells |
[93] |
| Brain Cancer | |||||
| In vitro | SNB19 and A1207 cells | 10, 15, 20 and 25 µM, 48 and 72 h | Suppressing proliferation, migration and invasion; Inducing apoptosis and cell cycle arrest |
↓NEDD4, Notch1, p-Akt; ↑G2/M phase |
[94] |
Abbreviations: ACSL4, acyl-CoA synthetase long-chain family member 4; Akt, protein kinase B; AKR1C2, Aldo-Keto reductase 1C2; ALP, alkaline phosphatase; AST, aspartate transaminase; ATF4, activating transcription factor 4; Atg3, autophagy related 3; Atg5, autophagy related 5; Bax, Bcl-2 associated X protein; BACH, BTB domain and CNC homolog 1; Bcl-2, B-cell lymphoma-2; Bim, Bcl-2 interacting mediator of cell death; Bcl-xL, B-cell lymphoma-extra-large; Caspase-3, cysteinyl aspartate specific proteinase 3; CDK1, cyclin dependent kinase 1; CDK4, cyclin dependent kinase 4; CDX2, caudal type homeobox 2; CHOP, C/EBP homologous protein; COX-2, cyclooxygenase-2; CYP11A1, Cytochrome P450scc; HSD3B2, type 2 3β-hydroxysteroid dehydrogenase; CYP17A1, Cytochrome P450(17α); DDIT3, DNA damage inducible transcript 3; DLC1, deleted in liver cancer 1; DNMT1, DNA methyltransferase 1; DNMT3a, DNA Methyltransferase 3 Alpha; ECM, extracellular matrix; ERCC1, excision repair cross-complementing gene; EGFR, phospho-epidermal growth factor receptor; eHSP70, extracellular HSP70; eIF2α, eukaryotic translation initiation factor-2α; EMT, Epithelial-mesenchymal transition; Epcam, epithelial cell adhesion molecule; ER stress, endoplasmic reticulum stress; ERK, extracellular regulated protein kinases; FTH1, ferritin heavy chain 1; G-CSF, granulocyte-colony stimulating factor; GFPu, a short degron CL1 fused to the COOH-terminus of green fluorescent protein; GM-CSF colony-stimulating factor; Gli1, Glioma-associated oncogene family zinc finger 1; Gli2, Glioma-associated oncogene family zinc finger 2; GPX4, glutathione peroxidase 4; GSH, glutathione; HO-1, hemeoxygenase-1; HSP70, heat shock protein 70; GST-π, glutathione thio-transferase π; HSPA5, heat shock 70 kDa protein 5; IL-1β, interleukin-1β; IL-6, interleukin-6; IKK, inhibitor of nuclear factor kappa-B kinase; JAK, Janus kinase; ITGB1, integrin beta 1; JNK, c-Jun N-terminal kinase; LC3, microtubule-associated protein light chain 3; MDA, malondialdehyde; MDSCs, myeloid-derived suppressor cells; MMP-2, matrix metalloprotein-2; MMP-9, matrix metalloprotein-9; MRP, multidrug resistance-related protein; mTOR, mammalian target of rapamycin; MyD88, myeloid differentiation primary response 88; Nanog, Nanog Homeobox; NEDD4, neural precursor cell expressed developmentally down-regulated protein 4; NFE2L2, NFE2-related factor 2; NNMT, Nicotinamide N-Methyltransferase; NF-κB, nuclear factor kappa-B; Nrf2, nuclear factor-erythroid 2-related factor-2; Oct4, Octamer-binding transcription factor 4; PARK7, Parkinson’s disease protein 7; P300, histone acetyltransferase p300; p38 MAPK, p38 mitogen-activated protein kinase; PARP, poly (ADP-ribose) polymerase; PCLAF, PCNA clamp associated factor; PD-1, Programmed cell death protein 1; PD-L1, Programmed death-ligand 1; PGE2, prostaglandin E2; PI3K, Phosphatidylinositol-3-kinase; P-gp, P-glycoprotein; PSMB, proteasome 20S subunit beta; PTEN, phosphatase and tensin homolog; PTP1B, Protein tyrosine phosphatase 1B; PTEN, Phosphatase and tensin homolog deleted on chromosome 10; PTCH1, Patched; PUMA, p53 upregulated modulator of apoptosis; RELA, v-rel reticulo-endotheliosis viral oncogene homolog A; ROS, Reactive oxygen species; sE-cad, soluble E-cadherin; SFRP5, secreted frizzled-related protein 5 gene; Smad2/3, SMAD family member 2/3; SMG1, suppressor of morphogenesis in genitalia 1; SMO, Smoothened; SOD, superoxide dismutase; Sox2, Sex determining region Y-box 2; SRD5A1, steroid 5α-reductase type 1; STAT, signal transducer and activator of transcription; StAR, steroidogenic acute regulatory protein; STAT3, signal transducer and activator of transcription 3; TCF4, transcription factor 4; TET1, tet methyl-cytosine dioxygenase 1; TGF-β, transforming growth factor beta; TIM-3, T-cell immunoglobulin and mucin-domain 3; TLR4, toll-like receptor 4; TNF-α, tumor necrosis factor α; Tregs, Regulatory T cells; TRAMP, the transgenic adenocarcinoma of the mouse prostate; USF1, upstream transcription factor 1;VEGF, vascular endothelial growth factor; Wnt3a, Wnt family member 3a; XIAP, X-linked inhibitor of apoptosis; Zeb1, Zinc finger E-box binding homeobox 1; ZO-1, zonula occludens-1; ΔΨm, mitochondrial membrane potential.