TABLE 2.
Molecular targets of synthetic bile acid derivatives against cancers.
| Bile acids | Derivatives | Cancer type | Cell line | Phenotype | Mechanism | Effects | Refs. |
|---|---|---|---|---|---|---|---|
| UDCA | HS-1030 | Colon cancers | HT-29 | Proliferation | Apoptosis | G1 phase arrest, sub-G1-fraction, cyclin D1, E and A and Cdk2, 4, and 6 decrease, Cdk inhibitor, p21WAF1/CIP1 increase | Park et al. (2004) |
| HS-1183 | Leukemia | Jurkat T cells | Proliferation | Apoptosis | Caspase-3 and -8 down-regulation, PARP cleavage, DNA fragmentation | Choi et al. (2001) | |
| Colon cancer | HT-29 | Proliferation | Apoptosis | Mentioned above | Park et al. (2004) | ||
| Cervical cancer | SiHa | Cell viability | Apoptosis | DNA fragmentation, Bax up-regulation, poly (ADP-ribose) polymerase cleavage | Im et al. (2005) | ||
| Breast cancer | MCF-7, MDA-MB-231 | Proliferation | Apoptosis | Apoptotic nuclear changes, sub-G1 population increase, DNA fragmentation | Im et al. (2001) | ||
| Prostate cancer | PC-3 | Proliferation | Apoptosis | DNA fragmentation, chromatin condensation, PARP cleavage, cell cycle arrest | Choi et al. (2003) | ||
| UDC-PTX | Leukemia | HL60, NB4 | Cell viability | Apoptosis | / | Melloni et al. (2022) | |
| Colon cancer | RKO, HCT116 | Cell viability | Apoptosis | / | Melloni et al. (2022) | ||
| CDCA | HS-1199 | Leukemia | Mentioned above | Choi et al. (2001) | |||
| Colon cancer | Mentioned above | Park et al. (2004) | |||||
| Cervical cancer | Mentioned above | Im et al. (2005) | |||||
| Breast cancer | Mentioned above | Im et al. (2001) | |||||
| Prostate cancer | Mentioned above | Choi et al. (2003) | |||||
| Gastric cancer | SNU-1 | Cell viability | Apoptosis | Mitochondrial changes, caspase-3 activation, DNA fragmentation, nuclear condensation | Moon et al. (2004) | ||
| Glioblastoma | U-118MG, U-87MG, T98G, U-373MG | Proliferation | Apoptosis | Mitochondria, caspases and proteasomes | Yee et al. (2005) | ||
| HS-1200 | Leukemia | Mentioned above | Choi et al. (2001) | ||||
| Colon cancer | Mentioned above | Park et al. (2004) | |||||
| Cervical cancer | Mentioned above | Im et al. (2005) | |||||
| Breast cancer | MCF-7, MDA-MB-231 | Proliferation | Apoptosis | p53 independent pathway activation | Im et al. (2001), Yee et al. (2007) | ||
| Prostate cancer | Mentioned above | Choi et al. (2003) | |||||
| Gastric cancer | SNU-1 | Cell viability | Apoptosis | Caspase- and mitochondria-dependent fashions | Moon et al. (2004), Jeong et al. (2003) | ||
| Glioblastoma | Mentioned above | Yee et al. (2005) | |||||
| Hepatocellular carcinoma | HepG2, Hep3B | Proliferation | Apoptosis | Egr-1 regulation | Liu et al. (2008), Park S. E. et al. (2008) | ||
| Thyroid carcinoma | KAT-18 | Cell viability | Apoptosis | Procaspase-3, procaspase-7, and poly (ADP)- ribose polymerase degradation, histone hyperacetylation induction, peripheral chromatin condensation, translocation of apoptosis-inducing factor and caspase-activated DNase decrease | Kim et al. (2009) | ||
| Compound IIIb | Multiple myeloma | KMS-11 | Cell viability | Apoptosis | Mcl-1 and PARP-1 cleavage, NF-kB signaling inhibition, DNA fragmentation | El Kihel et al. (2008) | |
| Glioblastoma multiforme | GBM | ||||||
| Colonic carcinoma | HCT-116 | ||||||
| ent-CDCA | Colon cancer | HT-29 and HCT-116 | Proliferation | Apoptosis | CD95 activation, ROS generation, procaspase-8 cleavage | Katona et al. (2009) | |
| CDC-PTX | Leukemia | Mentioned above | Melloni et al. (2022) | ||||
| Colon cancer | Mentioned above | Melloni et al. (2022) | |||||
| DCA | ent-DCA | Colon cancer | Mentioned above | Katona et al. (2009) | |||
| Compound 9 | Duodenal carcinoma | HuTu-80 | Cell viability | Apoptosis | ROS-dependent cell death | Markov et al. (2019) | |
| Hepatocellular carcinoma | HepG2 | ||||||
| Lung cancer | A549 | ||||||
| Cervical cancer | KB-3-1 | ||||||
| 4b, 4e, 4d | Lung cancer | A549 | Cell viability | Apoptosis | / | Patel et al. (2022) | |
| Cervical cancer | SiHa | ||||||
| 6g, 4e | Human osteosarcoma | HOS-CRL-1543 | Cell viability | / | / | Agarwal et al. (2018) | |
| 5-FU@Mic-Hyd | Skin cancer | L929, A375 | Cell viability | / | / | Pourmanouchehri et al. (2022) | |
| HD | Squamous cell carcinoma | SCC7 | Proliferation | Cytostatic and antiangiogenetic | Park K. et al. (2008) | ||
| Melanoma | B16F10 | ||||||
| LCA | ent-LCA | Colon cancer | Mentioned above | Katona et al. (2009) | |||
| LCA-PIP1 | Colon cancer | HCT-116, DLD-1, HCT-8 | Cell viability | Apoptosis | / | Singh et al. (2015) | |
| FHL | Nasopharyngeal carcinoma | KB | Cell viability | Apoptosis | Vessel density decrease | Yu et al. (2007) | |
| LCA acetate | Hepatoblastoma | HepG2 | Proliferation | Binding to VDR | Adachi et al. (2005) | ||
| Colon cancer | SW480 | Proliferation | Binding to VDR | ||||
| Leukemia | THP-1 | Monocytic differentiation | Binding to VDR | ||||
| Bile-acid- appended triazolyl aryl ketones | 6af and 6cf | Breast cancer | MCF-7 | Cell viability | / | Agarwal et al. (2021) | |
| CA | CA-Tam3- Am | Breast cancer | 4T1, MCF-7, T47D and MDA-MB-231 | Cell viability | Apoptosis | Molecular charge and hydrophobicity | Sreekanth et al. (2013) |
| LLC-202 | Liver cancer | HL7702 | Proliferation | / | / | Jiang et al. (2023) | |
| 6a, 6c, 6m | Breast cancer | MDAMB231 | Cell viability | / | / | Agarwal et al. (2016) | |
| Colon cancer | HT29 | ||||||
| 6e, 6i, 6m | Glioblastoma | U87 | |||||
| Piperazinyl bile acid derivative | 7b | Multiple myeloma | GBM, KMS-11 | Cell viability | Apoptosis | Nuclear and DNA fragmentation | Brossard et al. (2010) |
| Colon cancer | HCT-116 | ||||||
| Cationic bile acid-based facial amphiphiles featuring trimethyl ammonium head groups | LCA- TMA1, CDCA- TMA2, DCA- TMA2, and CA-TMA3 | Colon cancer | HCT-116 or DLD-1 | Proliferation | Apoptosis | Governing membrane interactions, translocation | Singh et al. (2013) |
| Bile acids | C-7 | Breast cancer | MCF-7, MDA-MB-231 | Cell viability | / | Bjedov et al. (2017) | |
| Pancreatic cancer | PC3 | ||||||
| Ovarian cancer | HeLa | ||||||
| Colon cancer | HT-29 | ||||||
| Compound 27 | Prostate cancer | PC3M | Proliferation | Cell cycle | G1 arrest | Mao et al. (2016) | |
| Colon cancer | HT-29 | ||||||
| Ovarian cancer | ES-2 | ||||||
| Cholic, ursodeoxycholic, chenodeoxycholic, deoxycholic and lithocholic acids | Piperazinyl bile carboxamide | Colon cancer | DLD-1, HCT-116, and HT-29 | Proliferation | / | Brossard et al. (2014) | |
HS-1030, and HS-1183, ursodeoxycholic acid derivatives; HS-1199, and HS-1200, chenodeoxycholic acid derivatives; ROS, reactive oxygen species; CA, cholic acid; CA-TMA3, cholic acid based amphiphile; CA-Tam3-Am, cholic acid−tamoxifen conjugate; CDCA, chenodeoxycholic acid; CDC-PTX, chenodeoxycholic-paclitaxel hybrid; CDCA-TMA2, chenodeoxycholic acid based amphiphiles; LCA, lithocholic acid; LCA-PIP1, lithocholic acid–piperidine 1; LCA-TMA1, lithocholic acid based amphiphile; norUDCA, nor-ursodeoxycholic acid; UDCA, ursodeoxycholic acid; UDC-PTX, ursodeoxycholic-paclitaxel hybrid; ent-CDCA, enantiomers of chenodeoxycholic acid; ent-DCA, enantiomers of deoxycholic acid; ent-LCA, enantiomers of lithocholic acid; 6af and 6cf, bile acid-added triazolyl aryl ketones; 7b, piperazinyl bile acid derivative; DCA, deoxycholic acid; DCA-TMA2, deoxycholic acid based amphiphiles; PARP, poly (ADP-ribose) polymerase; Mcl-1, myeloid leukemia 1; compound 9, chenodeoxycholic acid derivative; compound IIIb, chenodeoxycholic acid-substituted piperazine conjugate; VDR, vitamin D receptor; Egr-1, early growth response-1; p-ULK1, phosphorylation of Unc-51, like autophagy activating kinase 1; p-AMPK, phosphorylation of AMP-activated protein kinase; NF-κB, nuclear factor κappa-light-chain-enhancer of activated B cells.