Bile Acids and Liver Cancer: Molecular Mechanism and Therapeutic Prospects
Abstract
:1. Introduction
2. The Regulation of BA Metabolism
3. The Mechanism of BAs to Regulate HCC Development
3.1. The Association of Different Species of BAs with HCC
3.2. The Regulatory Effect of Various Species of BAs on Tumor Cells
3.3. The Role of BA Receptors in HCC Growth
3.4. The Effect of BA–Gut Microbiota Axis on HCC Development
3.5. The Link between BAs and Inflammation in HCC Development
3.6. The Effect of BAs on Immune Response to HCC
4. Prospects of BA-Based Therapeutics for HCC
4.1. BA Receptor Agonists
4.2. Modulation of BA Metabolism
4.3. Regulation of Gut Microbiota
4.4. Combination Therapy
5. Conclusions and Outlook
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Bile Acids | Cell Line | Effects | Ref |
---|---|---|---|
DCA | Huh-BAT, Huh-7, SNU-761, SNU-475 | Induction of apoptosis in NTCP-positive HCC cells, while inhibition of invasion of NTCP-negative HCC cells via NF-κB/COX-2/IL-8 signaling in combination with cyclooxygenase inhibitors | [42] |
UDCA | Huh-BAT, HepG2 | Inhibition of proliferation and induction of apoptosis via activation of ERK and dephosphorylation of STAT3 in synergy with sorafenib | [46] |
HepG2, BEL7402 | Inhibition of proliferation and induction of apoptosis via blocking cell cycle and regulating the expression of Bax/Bcl-2 genes | [47] | |
HepG2, SK-Hep1, SNU-423, Hep3B | Switch of oxaliplatin-induced necrosis to apoptosis via inhibiting of ROS production and activating of the p53-caspase 8 | [48] | |
Huh-BAT, SNU-761, SNU-475 | Suppression of cell growth and induction of DLC1 tumor suppressor protein expression | [49] | |
HepG2 | Induction of apoptosis via regulating the ratio of Bax/Bcl-2 and the expressions of Smac, Livin, and caspase-3 | [50] | |
Huh 7 | Iinhibition of angiogenesis through suppressing HIF-1α/VEGF/IL-8 | [45] | |
Obeticholic acid (OCA) | HepG2, Huh7, SNU-449 | Inhibition of proliferation, metastasis, and invasion through interfering IL-6/STAT3 | [51] |
GDCA | SUN-449, HepG2 | Inhibition of proliferation and migration, induction of apoptosis | [41] |
Bile Acids | Cell Line | Effects | Ref |
---|---|---|---|
CDCA | Huh-7, Hep3B | Enhancement of the TGF-β-induced EMT | [39] |
CDCA | Hep3B | Induction of Snail expression and downregulation of E-cadherin expression to induce migration and invasion | [40] |
LCA | Hep3B | Induction of Snail expression and downregulation of E-cadherin expression to induce migration and invasion | [40] |
Norcholic Acid (NorCA) | LM3, Huh-7 | Promotion of proliferation, migration, and invasion by negatively regulating FXR | [14] |
OCA | HepG2 | Induction of proliferation via stimulating MAFG expression | [52] |
GCDCA | HepG2 | Enhancement of antiapoptotic and proliferation by activating ERK1/2 inducing Mcl-1 phosphorylation at T163 to stabilize Mcl-1 protein | [53] |
SMMC-7721, Huh7 | Promotion of invasion via activating autophagy by targeting the AMPK/mTOR pathway | [54] |
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Zhang, X.; Shi, L.; Lu, X.; Zheng, W.; Shi, J.; Yu, S.; Feng, H.; Yu, Z. Bile Acids and Liver Cancer: Molecular Mechanism and Therapeutic Prospects. Pharmaceuticals 2024, 17, 1142. https://doi.org/10.3390/ph17091142
Zhang X, Shi L, Lu X, Zheng W, Shi J, Yu S, Feng H, Yu Z. Bile Acids and Liver Cancer: Molecular Mechanism and Therapeutic Prospects. Pharmaceuticals. 2024; 17(9):1142. https://doi.org/10.3390/ph17091142
Chicago/Turabian StyleZhang, Xuemei, Lei Shi, Xiaona Lu, Wenlan Zheng, Jia Shi, Shihan Yu, Hai Feng, and Zhuo Yu. 2024. "Bile Acids and Liver Cancer: Molecular Mechanism and Therapeutic Prospects" Pharmaceuticals 17, no. 9: 1142. https://doi.org/10.3390/ph17091142