Abstract
The search of alternative therapeutic agents for the use of cancer patients has dramatically expanded. Natural products are especially in focus since their structures already function in nature and are more likely to be potent with fewer side effects. Phloretin is a natural product that has been studied for a wide variety of pharmacological actions against human malignancies. This systematic review aims to present up-to-date critical and comprehensive information on the anti-cancer ability of Phloretin with all associated molecular and cellular mechanisms in various forms of cancers. Data retrieved according to PRISMA guidelines from Science Direct, PubMed, and Scopus searching servers by using keywords including Phloretin, cancer name, synergistic, resistance and Pharmacokinetics property was analyzed via some in silico tools. This systematic review comprised 127 articles from different types of study, where Phloretin is hypothesized to be effective against 20 various forms of cancer. Phloretin has been found to inhibit cancer initiation and progression by modulating many imbalanced signalling pathways, including apoptosis, autophagy, necrosis, metastasis, angiogenesis, cell proliferation, glucose absorption, oxidative stress, inflammation, DNA damage, and many other pathways. This wide range of activity may be due to the structural targeting of numerous proteins including, Bcl-2, Bax, Bak, Bad, caspase, cyclins (B1, D1, E) and CDKs (4, 6,7) p18, p21, p27, p53, MMP-2, MMP- 8, MMP-9, Wnt/-catenin, PARP, TNF-α, NF-κB, IκB kinase, IL-1β, TNF-α, phospho-Akt, phosphor-p65, NF-κB, PI3K/Akt, MAPK/ERK, p-mTOR. The introduction of nano-technology-based strategies can improve the efficacy of Phloretin for cancer treatment. Existing evidence shows that Phloretin has synergistic effects with other natural compounds and conventional drugs, and this mechanism assists in reversing the resistance of anticancer drugs by regulating resistance-related proteins. However, Phloretin possesses favorable pharmacokinetic properties with low toxicity in the human body by in silico methods. Therefore, Phloretin could be a potential anti-cancer drug against numerous cancer treatment by mitigating it's toxic effect and enhancing efficacy using nano-technology-based strategies.
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Abbreviations
- Bcl-2:
-
B-cell leukemia 2
- Bax:
-
Bcl-2-Associated X protein
- PI3K:
-
Phosphoinositide 3-kinase
- Akt:
-
Ak strain transforming
- mTOR:
-
Mammalian target of rapamycin
- MMP9 :
-
Matrix metalloproteinase 9
- GLUT:
-
Glucose transporters
- ULK1 :
-
Unc-51 like autophagy activating kinase
- ERK1/2:
-
Extracellular signal-regulated kinase 1/2
- TPA :
-
Tissue plasminogen activator
- LC3B :
-
Light chain 3B
- BCL-XL :
-
B-cell lymphoma-extra large
- XIAP :
-
X-linked inhibitor of apoptosis protein
- VEGF :
-
Vascular endothelial growth factor
- MTT :
-
3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide
- CAT :
-
Chloramphenicol acetyltransferase
- SOD :
-
Superoxide dismutase
- NF-B :
-
Nuclear factor-B
- Mac-1 :
-
Macrophage 1 antigen
- PEP :
-
Phosphoenolpyruvate
- GraB :
-
Granzyme B
- c-Myc :
-
Cellular Myc
- ROS :
-
Reactive oxygen species
- HCC :
-
Hepatocellular carcinoma
- SHP-1 :
-
Src homology region 2 domain-containing phosphatase-1
- STAT3 :
-
Signal transducer and activator of transcription 3
- pERK :
-
Protein kinase RNA-like endoplasmic reticulum kinase
- VEGFR :
-
Vascular endothelial growth factor receptor
- MAPK :
-
Mitogen-activated protein kinase
- CXCL12 :
-
C-X-C motif chemokine ligand 12
- CXCR4 :
-
C-X-C motif chemokine receptor 4
- TLR1 :
-
Toll-like receptor 1
- TLR2:
-
Toll-like receptor 2
- TNF-α :
-
Tumor necrosis factor-alpha
- NOD :
-
Nucleotide-binding oligomerization domain
- NLRP3:
-
Nucleotide-binding domain (NOD)-like receptor protein 3
- CDK4 :
-
Cyclin-dependent kinase 4
- CDK6 :
-
Cyclin-dependent kinase 6
- BAK :
-
Bcl-2 homologous antagonist/killer
- PARP :
-
Poly-ADP ribose polymerase
- HIF1 :
-
Hypoxia-inducible factor-1
- HKII :
-
Hexokinase 2
- PFKFB3 :
-
6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase isozyme 3
- PDHK1 :
-
Pyruvate dehydrogenase kinase 1
- LDH :
-
Lactate dehydrogenase
- Pink1 :
-
PTEN-induced kinase 1
- GSH:
-
Glutathione
- NSCLC :
-
Non-small cell lung cancer
- JNK :
-
C-Jun N-terminal kinase
- TRX:
-
Thioredoxin
- TXNIP :
-
Thioredoxin interacting protein
- 2-NBDLG :
-
2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-D-glucose
- PKC:
-
Protein kinase C
- Myt1 :
-
Myelin transcription factor 1
- cdc2:
-
Cyclin-dependent kinase 2
- HSP70:
-
70 Kilodalton heat shock protein
- IL-6:
-
Interleukin-6
- MRP:
-
Multi-drug resistance associated protein 1
- BCRP:
-
Breast cancer resistance protein
- MDR:
-
Multi-drug resistance
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Sohel, M., Nity, N.U., Sarker, M.R. et al. Exploring the chemotherapeutic potential and therapeutic insight of phloretin against human malignancies: a systematic review. Phytochem Rev (2024). https://doi.org/10.1007/s11101-024-09938-8
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DOI: https://doi.org/10.1007/s11101-024-09938-8