Abstract
Evodiamine is a major alkaloid component found in the fruit of Evodia rutaecarpa. It shows the anti-proliferative potential against a wide range of cancers by suppressing cell growth, invasion, and metastasis and inducing apoptosis both in vitro and in vivo. Evodiamine shows its anticancer potential by modulating aberrant signaling pathways. Additionally, the review focuses on several therapeutic implications of evodiamine, such as epigenetic modification, cancer stem cells, and epithelial to mesenchymal transition. Moreover, combinatory drug therapeutics along with evodiamine enhances the anticancer efficacy of chemotherapeutic drugs in various cancers by overcoming the chemo resistance and radio resistance shown by cancer cells. It has been widely used in preclinical trials in animal models, exhibiting very negligible side effects against normal cells and effective against cancer cells. The pharmacokinetic and pharmacodynamics-based collaborations of evodiamine are also included. Due to its poor bioavailability, synthetic analogs of evodiamine and its nano capsule have been formulated to enhance its bioavailability and reduce toxicity. In addition, this review summarizes the ongoing research on the mechanisms behind the antitumor potential of evodiamine, which proposes an exciting future for such interests in cancer biology.
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Abbreviations
- ROS:
-
Reactive oxygen species
- Top I:
-
Topoisomerase I
- CSC:
-
Cancer stem cell
- EMT:
-
Epithelial to mesenchymal transition
- DR:
-
Death receptor
- Akt:
-
Protein kinase B
- NF-κB:
-
Nuclear factor kappa-light-chain-enhancer of activated B
- SHH:
-
Sonic Hedgehog
- GLI1:
-
GLI family zinc finger 1
- cdk:
-
Cyclin-dependent kinase
- p:
-
Phosphorylated
- chk:
-
Checkpoint kinase
- DNMT:
-
DNA methyl transferase
- Notch3:
-
Neurogenic locus notch homolog protein 3
- mTOR:
-
Mammalian target of rapamycin
- S6K1:
-
Ribosomal protein S6 kinase beta-1
- Mcl-1:
-
Myeloid cell leukemia 1
- PARP :
-
Poly ADP ribose polymerase
- Nbk:
-
Natural born killer
- ER:
-
Estrogen receptor
- MEK:
-
Mitogen-activated protein kinase kinase
- ERK:
-
Extracellular-signal-regulated kinase
- PPAR:
-
Peroxisome proliferator-activated receptor gamma
- STAT3:
-
Signal transducer and activator of transcription 3
- SHP-1:
-
Src homology 2 domain-containing protein tyrosine phosphatase 1
- WWOX:
-
WWdomain-containing oxidoreductase
- VEGF:
-
Vascular endothelial growth factor
- NOD1:
-
Nucleotide-binding oligomerization domain-containing protein 1
- MAPK:
-
Mitogen-activated protein kinase
- YAP:
-
Yes-associated protein
- JNK:
-
C-Jun N-terminal kinase
- JAK2:
-
Janus Kinase 2
- MMP:
-
Matrix metallopeptidase
- Her-2:
-
Human epidermal growth factor receptor 2
- PLK1:
-
Polo-like kinase 1
- Wnt:
-
Wingless-related integration site
- IL:
-
Interleukin
- PERK:
-
Protein kinase R-like endoplasmic reticulum kinase
- PI3K:
-
Phosphatidylinositol 3-kinase
- NO:
-
Nitric oxide
- Mcl-1:
-
Myeloid cell leukemia 1
- SIRT1:
-
Sirtuin
- PKB:
-
Protein kinase B
- TGFβ:
-
Transforming growth factor beta
- Smad2:
-
Mothers against decapentaplegic homolog 2
- GADD45:
-
Growth arrest and DNA damage-inducible 45
- Mcm:
-
Minichromosome maintenance complex component
- TRADD:
-
Tumor necrosis factor receptor type 1-associated DEATH domain
- IRAK:
-
Interleukin-1 receptor-associated kinase
- cyt-c:
-
Cytochrome-c
- AIF:
-
Apoptosis-inducing factor
- ENDOG:
-
Endonuclease G
- c-Met:
-
Tyrosine-protein kinase Met
- Src:
-
Sarcoma
- Myt-1:
-
Myelin transcription factor 1
- miR:
-
MicroRNA
- NSCLC:
-
Non-small cell lung cancer
- PRAME:
-
Preferentially expressed antigen of melanoma
- HIF-1α:
-
Hypoxia-inducible factor 1-alpha
- IGF-1:
-
Insulin-like growth factor
- PTEN:
-
Phosphatase and tensin homolog
- cAMP:
-
Cyclic adenosine monophosphate
- TRAIL:
-
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand
- uPA:
-
Urokinase-type plasminogen activator
- COX-2:
-
Cyclooxygenase-2
- ICAM-1:
-
Intercellular cell adhesion molecule-1
- MDR:
-
Multidrug resistance
- XIAP:
-
X-linked inhibitor of apoptosis protein
- IAP:
-
Inhibitor of apoptosis protein
- FLIP:
-
Fas‐associated death domain (FADD)‐like IL‐1β‐converting enzyme‐inhibitory protein
- IkBα:
-
Nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha
- TNF:
-
Tumor necrosis factor
- IKK:
-
IκB kinase
- ABCG2:
-
ATP-binding cassette super-family G member 2
- LPS:
-
Lipopolysaccharide
- iNOS:
-
Inducible NOS
- CCA:
-
Cholangiocarcinoma
- PGI:
-
Phosphoglucose isomerase
- AMF:
-
Autocrine motility factor
- SHP:
-
Phosphatase shatterproof 1 N-terminal
- NBD:
-
Nucleotide binding domain
- HSP70:
-
Heat shock protein
- Sox2:
-
Sex determining region Y)-box 2
- KLF4:
-
Kruppel-like factor 4
- Oct4:
-
Octamer-binding transcription factor 4
- LRP5:
-
Low-density lipoprotein receptor-related protein 5
- SCD1:
-
Stearoyl-CoA desaturase
- HER:
-
Human epidermal growth factor receptor
- hes-5:
-
Hes family BHLH transcription factor 5
- Mst1/2:
-
Mammalian sterile 20-like kinase (MST) 1/2
- MET:
-
Mesenchymal to epithelial transition
- HGF:
-
Human growth factor
- TGF-β:
-
Transforming growth factor beta
- 5-aza:
-
5-Azacytidine
- TSA:
-
Trichostatin A
- AMPK:
-
5′ Adenosine monophosphate-activated protein kinase
- L-OHP:
-
Oxaliplatin
- HCT-116/L-OHP:
-
L-OHP resistant HCT-116
- CCRF-CEM/C1:
-
Camptothecin-resistant leukemic lymphoblast cells
- A2780R2000 :
-
Camptothecin-resistant A2780
- A2780/PTXR :
-
Paclitaxel resistant A2780
- ZJW:
-
Zuo-Jin-Wan
- 5-FU:
-
5-Fluorouracil
- Pt:
-
Platinum
- ERCC1:
-
Excision repair cross-complementing 1
- TS:
-
Thymidylate synthase
- HDAC:
-
Histone deacetylase
- H2AX:
-
H2A histone family member X
- DOX:
-
Doxorubicin
- LD50:
-
Lethal dose, 50%
- IC50 :
-
Inhibitory concentration, 50%
- T/NT ratio:
-
Tumor:nontumor ratio
- SUV:
-
Standardized uptake value
- AFP:
-
α-Fetoprotein
- CRC:
-
Colorectal cancer
- TSGF:
-
Tumor specific growth factor
- NEEPN:
-
Evodiamine-phospholipid nano complex
- MSNs:
-
Mesoporous silica nanoparticles
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Acknowledgements
The authors acknowledge the National Institute of Technology Rourkela, Odisha, India, for providing laboratory and other facilities to carry out this work.
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Department of Science and Technology, Science and Engineering Research Board (DST, SERB), New Delhi, India (Grant Number: ECR/2016/000792) and Ministry of human resource and development (MHRD), New Delhi, and Department of Science and Technology, Odisha, India (Grant No-1201).
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The first draft of the manuscript was prepared by MP. The bioavailability and pharmacokinetics section and Fig. 1 of this manuscript were written and drawn by SKT, and GZ edited the manuscript. BKB guided and edited the manuscript. Lastly, all authors approved the final version of the manuscript.
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Panda, M., Tripathi, S.K., Zengin, G. et al. Evodiamine as an anticancer agent: a comprehensive review on its therapeutic application, pharmacokinetic, toxicity, and metabolism in various cancers. Cell Biol Toxicol 39, 1–31 (2023). https://doi.org/10.1007/s10565-022-09772-8
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DOI: https://doi.org/10.1007/s10565-022-09772-8