Abstract
Purpose
This paper reviews marine compounds that target the mitogen-activated protein kinase (MAPK) signaling pathway and their main sources, chemical structures, major targeted cancers and possible mechanisms to provide comprehensive and basic information for the development of marine compound-based antitumor drugs in clinical cancer therapy research.
Methods
This paper searched the PubMed database using the keywords “cancer”, “marine*” and “MAPK signaling pathway”; this search was supplemented by the literature-tracing method. The marine compounds screened for review in this paper are pure compounds with a chemical structure and have antitumor effects on more than one tumor cell line by targeting the MAPK signaling pathway. The PubChem database was used to search for the PubMed CID and draw the chemical structures of the marine compounds.
Results
A total of 128 studies were searched, and 32 marine compounds with unique structures from extensive sources were collected for this review. These compounds are cytotoxic to cancer cell lines, although their targets are still unclear. This paper describes their anticancer effect mechanisms and the protein expression changes in the MAPK pathway induced by these marine compound treatments. This review is the first to highlight MAPK signaling pathway-targeted marine compounds and their use in cancer therapy.
Conclusion
The MAPK signaling pathway is a promising potential target for cancer therapy. Searching for marine compounds that exert anticancer effects by targeting the MAPK signaling pathway and developing them into new marine anticancer drugs will be beneficial for cancer treatment.
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Abbreviations
- AKT:
-
Protein kinase B
- CDC:
-
Cell division cycle
- Csps:
-
Colonospheres
- Cyt C:
-
Cytochrome C
- DR5:
-
Death receptor 5
- EGFR:
-
Epidermal growth factor receptor
- EMA:
-
European Medicines Agency
- EMT:
-
Epithelial–mesenchymal transition
- ERK:
-
Extracellular signal-regulated kinase
- FADD:
-
Fas-associating protein with a novel death domain
- GRB2:
-
Growth factor receptor-bound protein 2
- HCC:
-
Hepatocellular carcinoma
- HIF-1α:
-
Hypoxia inducible factor-1α
- IGF:
-
Insulin-like growth factor
- JNK:
-
C-Jun N-terminal kinase
- MAPK:
-
Mitogen-activated protein kinase
- MEK:
-
Mitogen-activated protein kinase kinase
- MEKK4:
-
Mitogen-activated protein kinase kinase kinase 4
- MKK3:
-
Mitogen-activated protein kinase kinase 3
- MMP:
-
Mitochondrial membrane potential
- MMP-2/-9:
-
Matrix metalloproteinase 2/9
- mTOR:
-
Mammalian target of rapamycin
- NF-κB:
-
Nuclear factor kappa-B
- NSCLC:
-
Nonsmall cell lung cancer
- PARP:
-
Polymerase (ADP-ribose) polymerase
- PI3K:
-
Phosphatidylinositol 3 kinase
- PIM2:
-
Recombinant Pim-2 Oncogene
- PKC:
-
Protein kinase C
- ROS:
-
Reactive oxygen species
- SAPK:
-
Stress-activated protein kinase
- TNBC:
-
Triple-negative breast cancer
- TRAIL:
-
Tumor necrosis factor-related apoptosis-inducing ligand
- uPA:
-
Urokinase-type plasminogen activator
- FxOH:
-
Fucoxanthinol
- Lam:
-
Laminarin
- SA:
-
Salternamide A
- Mer:
-
Mertensene
- SE11:
-
1′-Deoxyrhodoptilometrin
- SE16:
-
(S)-(−)-Rhodoptilometrin
- SB:
-
Siphonodictyal B
- (19Z)-HCA:
-
(19Z)-Halichondramide
- Apl:
-
Aplysin
- Asp A:
-
Asperolide A
- DA:
-
Dihydroaustrasulfone alcohol
- C800:
-
Crambescidin 800
- C828:
-
Aurantoside C
- Lep A:
-
Leptaochotensosides A
- FC:
-
Fumigaclavine C
- Pli:
-
Plitidepsin
- MA:
-
Mycalamide A
- Pt-A:
-
Ptilomycalin A
- Pch-A:
-
Pulchranin A
- 12-dea-12-ES:
-
12-Deacetyl-12-epi-scalaradial
- Fuc:
-
Fucoidan
- Momc:
-
Monanchoxymycalin c
- FX:
-
Fucoxanthin
- STD:
-
Stichoposide D
- 11-epi-SA:
-
11-Epi-sinulariolide acetate
- WB:
-
Wentilactone B
- EPA:
-
Eupalmerin acetate
- BBA:
-
Bisebromoamide
- GA:
-
Gentisyl alcohol
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We thank American Journal Experts for their help in revising the English grammar.
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This work was supported by the National Natural Science Foundation of China (31770774), the Provincial Major Project of Basic or Applied Research in Natural Science, Guangdong Provincial Education Department (2016KZDXM038) and the Higher Education Reform Project of Guangdong Province (2019268).
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ZH and JW contributed to the design and conception of the study; RL and XH performed the information retrieval and analysis; JW, RL, XH, TL and ZZ wrote the manuscript; TL and ZZ created the table and figures; and ZH guided the manuscript writing and provided financial support. Additionally, all the authors read and approved the final manuscript.
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Figure S.
Flow diagram of the process to select eligible studies; “n” represents the number of studies retrieved (TIF 8267 KB)
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Wei, J., Liu, R., Hu, X. et al. MAPK signaling pathway-targeted marine compounds in cancer therapy. J Cancer Res Clin Oncol 147, 3–22 (2021). https://doi.org/10.1007/s00432-020-03460-y
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DOI: https://doi.org/10.1007/s00432-020-03460-y