TABLE 1.
Tumor suppressive effects of natural BAs on cancers.
| Cancer types | Cell lines | Bile acids | Phenotype | Effects | Refs |
|---|---|---|---|---|---|
| Glioblastoma | A172, LN229 | UDCA | Cell viability | Inducing ROS production, arresting the G1 phase, reducing MMP and inducing endoplasmic reticulum stress | Yao et al. (2020) |
| Neuroblastoma | BE (2)-m17, SK-n-SH, SK-n-MCIXC and Lan- 1 | LCA | Cell death | Activating apoptotic pathways | Goldberg et al. (2011) |
| WT CLS1, SK NEP1 | LCA | Proliferation | Activating apoptotic pathways | Trah et al. (2020) | |
| Oral Squamous Carcinoma | HSC-3 | UDCA | Cell viability | Inducing apoptosis via caspase activation | Pang et al. (2015) |
| Pancreatic cancer | HPAC, Capan1 | UDCA | EMT, stem cell formation | Upregulating intracellular ROS and down-regulating Prx2 | Kim E. K. et al. (2017) |
| PANC-1 | Bile acids | Proliferation, EMT | Inducing apoptosis via ROS and EMT pathway | Zhu et al. (2022) | |
| PANC-1, MIA PaCa-2, PGHAM-1 | DCA, CA | Proliferation, cytoplasmic microvilli loss and organelles vacuolization | Increasing the percentage of G0+G1 phase cells | Wu et al. (2003) | |
| GCA, TDCA | Proliferation, cytoplasmic microvilli loss and organelles vacuolization | Elevating the S phase cell number | Wu et al. (2003) | ||
| Prostate cancer | DU145 | UDCA | Proliferation | Activating apoptotic pathways | Lee et al. (2017) |
| LNCaP, PC-3 | LCA | Proliferation | Activating apoptotic pathways | Goldberg et al. (2013) | |
| PC-3, DU145 | LCA | Cell viability | Inducing ER stress, autophagy, and mitochondrial dysfunction | Gafar et al. (2016) | |
| LNCaP, DU145 | CDCA | Proliferation | Activating FXR and accumulating lipids via the SREBF pathway | Liu et al. (2016) | |
| LNCaP | CDCA | Proliferation | Activating FXR and upregulating PTEN. | Liu et al. (2014) | |
| Hepatocellular carcinoma | Huh-BAT, HepG2 | UDCA | Proliferation | Activating ERK and dephosphorylating STAT3 | Lee et al. (2018) |
| B16-F10, MC38, LLC, A549 and SW480 | UDCA | Treg cell differentiation and activation | Enhancing antitumor immunity by serving as a TGF-β inhibitor | Shen et al. (2022) | |
| HepG2 | TUDCA | Proliferation and invasion | Suppressing cell death and inflammation mediated by ER stress | Vandewynckel et al. (2015) | |
| HepG2, BEL7402 | UDCA | Proliferation | Blocking the cell cycle and regulating the expression of Bax/Bcl-2 genes | Liu et al. (2007), Liu et al. (2015) | |
| HepG2 | UDCA | Proliferation | Inducing apoptosis via regulation of the expressions of Smac and Livin and caspase 3 | Zhu et al. (2014) | |
| Huh-Bat, SNU761, SNU475 | UDCA | Proliferation | Inhibiting proteasomal DLC1 degradation | Chung et al. (2011) | |
| HepG2, SK-Hep1, SNU-423, Hep3B | UDCA | Proliferation | Inhibiting ROS production and activating the p53-caspase 8 pathway | Lim et al. (2010) | |
| HepG2, Huh7, mouse hepatoma Hepa 1–6 | CDCA | / | Inducing NDRG2 expression through FXR receptor | Langhi et al. (2013) | |
| Gastric cancer | MKN-74 | UDCA | Invasion | Suppressing chenodeoxycholic acid-induced PGE2 production | Wu et al. (2018) |
| SNU601, SNU638 | UDCA | Proliferation | Inducing apoptosisthrough the expression and activation of DR5 | Lim et al. (2011) | |
| SGC-7901 | TUDCA | Proliferation, invasion | Inducing Apoptosis | Zhang et al. (2022) | |
| SCM1 | DCA | Cell viability | Causing Ca (2+)-independent apoptosis | Chien et al. (2015) | |
| SGC-7901 | DCA | Proliferation | Inducing apoptosis through the mitochondrial-dependent pathway | Song et al. (2013) | |
| SNU601 | UDCA | Proliferation | Inducing apoptosis via MEK (MAPK)/ERK pathway | Lim et al. (2012) | |
| SNU601 | UDCA | Proliferation | Inducing apoptosis via CD95/Fas death receptor, downregulating ATG5 level and preventing autophagic pathway | Lim and Han (2015) | |
| BGC-823 | DCA | Proliferation | Activating p53 mediated pathway | Yang et al. (2015) | |
| SNU-216, MKN45 | DCA | Invasion, migration | Inducing MUC2 expression | Pyo et al. (2015) | |
| Oesophageal cancer | SKGT-4, OE33 | UDCA | / | Inhibiting NF-κB, AP-1 activation and COX-2 upregulation | Abdel-Latif et al. (2016) |
| Colon cancer | HCT116 | UDCA | Apoptosis | Modulating EGFR/Raf-1/ERK signaling | Im and Martinez (2004) |
| HCT116 | UDCA | Apoptosis | Mediating the PI3K, MAPK, or cAMP pathways | Saeki et al. (2012) | |
| HCT116 | UDCA | Proliferation | Inhibiting the expression of c-Myc and cell cycle regulatory molecules | Peiró-Jordán et al. (2012) | |
| HT29, HCT116 | UDCA | Proliferation | Regulating ROS production, activating ERK1/2 | Kim Y. J. et al. (2017) | |
| HCT116 | UDCA | Progression | Inhibiting interleukin β1 and blocking NF-κB and AP-1 activation | Shah et al. (2006) | |
| HT-29 | UDCA | Proliferation | Promoting endocytosis and degradation of EGFR receptor | Feldman and Martinez (2009) | |
| HCT116, COLO 205 | TUDCA | Progression | Suppressing NF-κB signaling | Kim et al. (2019) | |
| Caco-2, HT29C19A | LCA | Anti-inflammatory signals | Blocking inflammatory signals | Sun et al. (2008) | |
| HCT116 | LCA | Proliferation | Activating p53 and binding to MDM4 and MDM2 | Vogel et al. (2012) | |
| HCT116 | DCA, CDCA | Proliferation | Induce apoptosis | Powell et al. (2001) | |
| HCT116 | DCA | Proliferation | Inducing apoptosis via AP-1 and C/EBP mediated GADD153 expression | Qiao et al. (2002) | |
| HCT116 | DCA | Proliferation | Inhibiting cell growth and inducing apoptosis physiologically | Zeng et al. (2015) | |
| Cholangiocarcinoma | Mz-ChA-1 | TUDCA | Proliferation | Involving in MAPK p42/44 and PKCα | Alpini et al. (2004) |
| Gallbladder cancer | NOZ, GBC-SD, EH-GB1 | DCA | Proliferation | Interfering with miR-92b-3p maturation | Lin et al. (2020) |
| NOZ, EH-GB1 | LCA | Proliferation | Downregulating GLS-mediated glutamine metabolism and inducing ferroptosis | Li et al. (2022) | |
| Breast cancer | MCF7, MDA-MB-231 | LCA | Proliferation | Inducing TGR5 expression, inhibiting lipogenesis and reducing ERα expression | Luu et al. (2018) |
| MCF7, 4T1 | LCA | Proliferation, EMT, VEGF production, immune response | Activating TGR5 receptor | Mikó et al. (2018) | |
| MCF7, 4T1 | LCA | Oxidative stress | Inducing NRF2/NFE2L2 dependent oxidative/nitrosative stress | Kovács et al. (2019) | |
| MCF7 | CDCA | Tamoxifen-resistance | Activating FXR receptor | Giordano et al. (2011) | |
| MCF7, MDA-MB-231 | CDCA | Cell death | Activating FXR receptor | Alasmael et al. (2016) | |
| Ovarian cancer | OVCAR3 | CDCA, DCA | Proliferation | Upregulating BRCA1 and downregulating ESR1 gene expression | Jin et al. (2018) |
| A2780 | CDCA, DCA | Proliferation | Inducing apoptosis | Horowitz et al. (2007) | |
| Leukemia | T leukemia cell line | UDCA, TUDCA | Proliferation | Delaying cell cycle progression | Fimognari et al. (2009) |
| THP1, Molm-13 | CDCA | Proliferation, inhibition of M2 macrophage polarization | Accumulating LDs and lipid peroxidation via ROS/p38 MAPK/DGAT1 pathway | Liu et al. (2022) | |
| HL60, THP-1 | DCA, CDCA, LCA | Proliferation and differentiation | Accumulating the G0/G1 transition and inhibiting the differentiation | Zimber et al. (1994) | |
| Melanoma | M14, A375 | UDCA | Proliferation | Inducing ROS-triggered mitochondrial-associated pathway | Yu et al. (2019) |
GCA, glycocholic acid; TDCA, taurodeoxycholic acid; UDCA, ursodeoxycholic acid; TUDCA, tauroursodeoxycholic acid; ROS, reactive oxygen species; LCA, lithocholic acid; EMT, epithelial–mesenchymal transition; DCA, deoxycholic acid; CA, cholic acid; CDCA, chenodeoxycholic acid; Prx2, peroxiredoxin II; FXR, farnesoid X receptor; Dlc1, deleted in Liver Cancer 1; AP-1, activator protein-1; COX2, cyclooxygenase-2; Bax, Bcl-2-associated X protein; Bcl-2, B-cell lymphoma 2; PGE2, prostaglandin E2; MDM2, mouse double minute 2; MDM4, double Minute 4; c-Myc, myc-Related translation/localization regulatory factor; ERK, extracellular signal-regulated kinase; MAPK, mitogen-activated protein kinase; NF-κB, nuclear factor κappa-light-chain-enhancer of activated B cells; PI3K, phosphatidylinositol 3-kinase; STAT3, signal transducer and activator of transcription 3; TGR5, G protein-coupled bile acid receptor 5; VEGF, vascular endothelial growth factor; DR5, death receptor 5; NDRG2, N-Myc downstream regulated gene 2; SREBF, sterol regulatory element-binding factor; MUC2, mucin 2; ATG5, Autophagy Related 5; cAMP, cyclic adenosine monophosphate; GADD153, growth arrest- and DNA, damage-inducible gene 153; BRCA1, breast cancer type 1 susceptibility protein; PTEN, phosphatase and tensin homolog; EGFR, epithelial growth factor receptor; C/EBP, CCAAT/enhancer-binding protein beta; RAF1, Raf-1, Proto-Oncogene; NRF2, nuclear factor erythroid 2-related factor 2; LDs, lipid droplets; PKCα, protein kinase C α; MMP, mitochondrial membrane potential; GLS, glutaminase; TGF-β, Transforming growth factor-β; Smac, second mitochondria-derived activator of caspase; ESR1, Estrogen Receptor 1.