Computational biology and in vitro studies for anticipating cancer-related molecular targets of sweet wormwood (Artemisia annua).
Artemisia annua
Cancer
Dynamic simulation
Molecular docking
Network pharmacology
Journal
BMC complementary medicine and therapies
ISSN: 2662-7671
Titre abrégé: BMC Complement Med Ther
Pays: England
ID NLM: 101761232
Informations de publication
Date de publication:
08 Sep 2023
08 Sep 2023
Historique:
received:
31
05
2023
accepted:
21
08
2023
medline:
11
9
2023
pubmed:
9
9
2023
entrez:
8
9
2023
Statut:
epublish
Résumé
Cancer is one of the leading causes of death worldwide. Recently, it was shown that many natural extracts have positive effects against cancer, compared with chemotherapy or recent hormonal treatments. A. annua is an annual medicinal herb used in the traditional Chinese medicine. It has also been shown to inhibit the proliferation of various cancer cell lines. Multi-level modes of action of A. annua constituents in cancer therapy were investigated using an integrated approach of network pharmacology, molecular docking, dynamic simulations and in-vitro cytotoxicity testing on both healthy and cancer cells. Network pharmacology-based analysis showed that the hit Artemisia annua constituents related to cancer targets were 3-(2-methylpropanoyl)-4-cadinene-3,11-diol, artemisinin G, O-(2-propenal) coniferaldehyde, (2-glyceryl)-O-coniferaldehyde and arteamisinin III, whereas the main cancer allied targets were NFKB1, MAP2K1 and AR. Sixty-eight significant signaling KEGG pathways with p < 0.01 were recognized, the most enriched of which were prostate cancer, breast cancer, melanoma and pancreatic cancer. Thirty-five biological processes were mainly regulated by cancer, involving cellular response to mechanical stimulus, positive regulation of gene expression and transcription. Molecular docking analysis of the top hit compounds against the most enriched target proteins showed that 3-(2-methylpropanoyl)-4-cadinene-3,11-diol and O-(2-propenal) coniferaldehyde exhibited the most stabilized interactions. Molecular dynamics simulations were performed to explain the stability of these two compounds in their protein-ligand complexes. Finally, confirmation of the potential anticancer activity was attained by in-vitro cytotoxicity testing of the extract on human prostate (PC-3), breast (MDA-MB-231), pancreatic (PANC-1) and melanoma (A375) cancerous cell lines. This study presents deeper insights into A. annua molecular mechanisms of action in cancer for the first time using an integrated approaches verifying the herb's value.
Sections du résumé
BACKGROUND
BACKGROUND
Cancer is one of the leading causes of death worldwide. Recently, it was shown that many natural extracts have positive effects against cancer, compared with chemotherapy or recent hormonal treatments. A. annua is an annual medicinal herb used in the traditional Chinese medicine. It has also been shown to inhibit the proliferation of various cancer cell lines.
METHODS
METHODS
Multi-level modes of action of A. annua constituents in cancer therapy were investigated using an integrated approach of network pharmacology, molecular docking, dynamic simulations and in-vitro cytotoxicity testing on both healthy and cancer cells.
RESULTS
RESULTS
Network pharmacology-based analysis showed that the hit Artemisia annua constituents related to cancer targets were 3-(2-methylpropanoyl)-4-cadinene-3,11-diol, artemisinin G, O-(2-propenal) coniferaldehyde, (2-glyceryl)-O-coniferaldehyde and arteamisinin III, whereas the main cancer allied targets were NFKB1, MAP2K1 and AR. Sixty-eight significant signaling KEGG pathways with p < 0.01 were recognized, the most enriched of which were prostate cancer, breast cancer, melanoma and pancreatic cancer. Thirty-five biological processes were mainly regulated by cancer, involving cellular response to mechanical stimulus, positive regulation of gene expression and transcription. Molecular docking analysis of the top hit compounds against the most enriched target proteins showed that 3-(2-methylpropanoyl)-4-cadinene-3,11-diol and O-(2-propenal) coniferaldehyde exhibited the most stabilized interactions. Molecular dynamics simulations were performed to explain the stability of these two compounds in their protein-ligand complexes. Finally, confirmation of the potential anticancer activity was attained by in-vitro cytotoxicity testing of the extract on human prostate (PC-3), breast (MDA-MB-231), pancreatic (PANC-1) and melanoma (A375) cancerous cell lines.
CONCLUSION
CONCLUSIONS
This study presents deeper insights into A. annua molecular mechanisms of action in cancer for the first time using an integrated approaches verifying the herb's value.
Identifiants
pubmed: 37684586
doi: 10.1186/s12906-023-04135-0
pii: 10.1186/s12906-023-04135-0
pmc: PMC10492370
doi:
Substances chimiques
coniferaldehyde
06TPT01AD5
Acrolein
7864XYD3JJ
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
312Informations de copyright
© 2023. BioMed Central Ltd., part of Springer Nature.
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