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New Phenylpropanoid from Croton velutinus (Euphorbiaceae) as Potential Anticancer Natural Product Targeting MAPKs:
Renata A de Abrantes1, Natalia F de Sousa1, Ana Paula G M Farias1
1Postgraduate Program in Natural Products and Bioactive Synthetics, Federal University of Paraíba, João Pessoa, 58051-970, PB, Brazil.
Abstract:
Cancer encompasses a group of diseases characterized by uncontrolled cell growth and the ability to invade or spread to other parts of the body. It is considered a major public health issue, being the second leading cause of death worldwide. A crucial signaling pathway altered in many cancers is the Mitogen- Activated Protein Kinase (MAPK) pathway, which is associated with the regulation of cell proliferation, differentiation, and survival, playing a central role in the development and maintenance of malignant tumors. Natural products have made significant contributions to pharmacotherapy, particularly in the field of cancer treatment. The Euphorbiaceae family, comprising approximately 300 genera and over 5,000 species, is known for its rich diversity of bioactive compounds. Croton velutinus (Euphorbiaceae), a species predominantly found in Northeast Brazil, has recently garnered attention due to its novel phenylpropanoids isolated from its roots. Among these, (E)-4-(1-epoxy-7,8-propen) phenylbenzoate (CV2) has demonstrated potential cytotoxic activity against various human tumor cell lines, including B16F10, MCF-7, HL60, HCT-116, and HepG2. This review aims to highlight the antitumor activity of phenylpropanoids derived from the Euphorbiaceae family. Furthermore, through molecular docking studies, we explored the binding efficacy of CV2 with MAPKs (ERK, JNK, p38), comparing it to 25 other phenylpropanoid compounds reported in the literature, revealing promising interactions that could be further investigated for therapeutic applications.
Insights
Phenylpropanoids from the Euphorbiaceae family show promise as cancer treatments. Compound CV2 from Croton velutinus exhibits cytotoxic activity and favorable interactions with cancer-related Mitogen-Activated Protein Kinase (MAPK) pathways.
Area of Science:
- Natural product chemistry
- Cancer biology
- Pharmacology
Background:
- Cancer is a leading global cause of death, with the Mitogen-Activated Protein Kinase (MAPK) pathway critically involved in tumor development.
- Natural products, particularly from the Euphorbiaceae family, offer a rich source of potential anticancer agents.
- Croton velutinus, a Brazilian plant, yields novel phenylpropanoids with demonstrated cytotoxic effects.
Purpose of the Study:
- To review the antitumor activities of Euphorbiaceae-derived phenylpropanoids.
- To investigate the molecular interactions of the phenylpropanoid CV2 with key MAPK pathway proteins.
- To compare CV2's binding efficacy with other known phenylpropanoids against MAPKs.
Main Methods:
- Literature review of phenylpropanoids from the Euphorbiaceae family with antitumor activity.
- Cytotoxicity assays of CV2 against multiple human cancer cell lines (B16F10, MCF-7, HL60, HCT-116, HepG2).
- Molecular docking simulations to assess CV2 and other phenylpropanoids' binding affinity to MAPK proteins (ERK, JNK, p38).
Main Results:
- CV2 demonstrated significant cytotoxic activity across a panel of human tumor cell lines.
- Molecular docking revealed that CV2 exhibits promising binding interactions with MAPK pathway components.
- CV2's interactions with MAPKs were competitive when compared to 25 other studied phenylpropanoids.
Conclusions:
- Phenylpropanoids from the Euphorbiaceae family, including CV2 from Croton velutinus, possess significant antitumor potential.
- CV2's interaction with MAPK pathways suggests a viable mechanism for its cytotoxic effects.
- Further research into CV2 and related compounds could lead to novel cancer therapeutics targeting the MAPK pathway.
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