Prostate Cancer—Focus on Cholesterol
Abstract
:Simple Summary
Abstract
1. Introduction
2. Prostate Metabolism
3. Cholesterol Function and Prostate Cell Supply
4. Regulation of Cholesterol Homeostasis
5. Cholesterol Profile in Blood
6. Cholesterol Profile in the Prostate Tissue
7. Dysregulated Signaling Pathways in Prostate Cancer
7.1. P53 and SREBP2
7.2. AR (Androgen Receptor)
7.3. PI3K/AKT/MTOR
7.4. MAPK
8. Acidity
9. SREBP2 Targets
10. Cholesterol-Lowering Drugs and HDL Particles
11. Perspective
12. Conclusions
- increased membrane/lipid rafts synthesis and protein prenylation which alter membrane composition and cell signaling
- mut p53 stabilization and further mevalonate pathway promotion
- nucleotide synthesis, mitochondrial electron transport, protein anchoring and stabilization, ferroptosis inhibition
- intracellular androgen synthesis
- SREBP2 interaction with Myc promoter
Author Contributions
Funding
Conflicts of Interest
Abbreviations
ABCA1 | ATP-binding cassette transporter A1 |
ABCG1 | ATP-binding cassette transporter G |
ACLY | ATP citrate lyase |
AMPK | AMP-activated protein kinase |
AR | Androgen receptor |
ARE | Androgen responsive element |
BCR | Biochemical recurrence |
BPH | Benign prostatic hyperplasia |
COPII | Coatomer II |
CRPC | Castrate-resistant prostate cancer |
DHT | Dihydrotestosterone |
EGFR | Epidermal growth factor receptor |
ERK | Extracellular signal-regulated kinase |
FA | Fatty acid |
FDG-PET | Fluorodeoxyglucose-positron emission tomography |
FPP | Farnesyl diphosphate |
GGPP | Geranyl-geranyl-pyrophosphate |
GSK3 | Glycogen synthase kinase 3 |
HDL | High-density lipoprotein |
HMG-CoA | 3-hydroxy-3methylglutaryl-CoA |
INSIG | Insulin-induced gene |
ICMT | Isoprenylcysteine carboxyl methyltransferase |
LDL | Low-density lipoprotein |
LDLR | Low-density lipoprotein receptor |
LRP8 | Lipoprotein receptor-related proteins 8 |
LXR | Liver X receptor |
MAPK | Mitogen-activated protein kinase |
mTOR | Mechanistic target of rapamycin |
PC | Prostate cancer |
PSA | Prostate-specific antigen |
ROS | Reactive oxygen species |
S1P | Site-1 protease |
S2P | Site-2 protease |
SCAP | SREBP cleavage-activating protein |
SHBG | Sex hormone-binding globulin |
SQLE | Squalene monooxygenase |
SR-B1 | Scavenger receptor class B member 1 |
SRE | Sterol response element |
SREBP2 | Sterol regulatory element–binding protein-2 |
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Drug | Target | Function | Reference |
---|---|---|---|
Statins (in general) | HMGCR | Reduces HMG-CoA to mevalonate | [143] |
Atorvastatin | SLCO2B1 | Androgen transporting gene (uptake) | [139] |
DNAJA1 | Cochaperone protein (protects mut p53 form degradation) | [143] | |
Pravastatin | SLCO2B1 | Androgen transporting gene (uptake) | [139] |
Fatostatin | SCAP | SREBP2 and SREBP1 maturation | [145] |
Tubulin | Maintenance of microtubule organization | [145] | |
Lovastatin | DNAJA1 | Cochaperone protein (protects mut p53 form degradation) | [143] |
Mevastatin | DNAJA1 | Cochaperone protein (protects mut p53 form degradation) | [143] |
Betulin | SCAP-INSIGN interaction | SCAP/SREBP translocation | [147] |
Xanthohumol | Sec23/24 (COPII vesicle) | SCAP/SREBP translocation | [146] |
Combination therapy | |||
Statins + Dipyridamole (antiplatelet agent) | Phosphodiesterase | Hydrolysis of cyclic nucleotides | [84,152] |
Simvastin + enzalutamide (antiandrogen) | AR | Activation of AR signaling pathway | [74] |
Fatostatin + Docetaxel (chemotherapeutic agent) | Tubulin | Maintenance of microtubule organization | [98,153] |
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Škara, L.; Huđek Turković, A.; Pezelj, I.; Vrtarić, A.; Sinčić, N.; Krušlin, B.; Ulamec, M. Prostate Cancer—Focus on Cholesterol. Cancers 2021, 13, 4696. https://doi.org/10.3390/cancers13184696
Škara L, Huđek Turković A, Pezelj I, Vrtarić A, Sinčić N, Krušlin B, Ulamec M. Prostate Cancer—Focus on Cholesterol. Cancers. 2021; 13(18):4696. https://doi.org/10.3390/cancers13184696
Chicago/Turabian StyleŠkara, Lucija, Ana Huđek Turković, Ivan Pezelj, Alen Vrtarić, Nino Sinčić, Božo Krušlin, and Monika Ulamec. 2021. "Prostate Cancer—Focus on Cholesterol" Cancers 13, no. 18: 4696. https://doi.org/10.3390/cancers13184696