Fruticuline A, a chemically-defined diterpene, exerts antineoplastic effects in vitro and in vivo by multiple mechanisms

Natural products have been recognized as important bioactive compounds on the basis of their wide biological properties. Here we investigated the antitumor effect and molecular mechanisms of the diterpene Fruticuline A (fruti) from Salvia lachnostachys , in human cancer cell lineages and Solid Ehrli...

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Veröffentlicht in:Scientific reports Jg. 10; H. 1; S. 16477
Hauptverfasser: Corso, Claudia Rita, Stipp, Maria Carolina, Radulski, Débora Rasec, Mariott, Marihá, da Silva, Luisa Mota, de Souza Ramos, Edneia Amancio, Klassen, Giseli, Queiroz Telles, José Ederaldo, Oliveira, Cristhian Santos, Stefanello, Maria Élida Alves, Verhoeven, Arthur J., Oude Elferink, Ronald P. J., Acco, Alexandra
Format: Journal Article
Sprache:Englisch
Veröffentlicht: London Nature Publishing Group UK 05.10.2020
Nature Publishing Group
Schlagworte:
631/154/436
631/67/1059
692/4028
Angiogenesis
Animals
Antineoplastic Agents - pharmacology
Antitumor activity
Apoptosis
Apoptosis - drug effects
Bcl-2 protein
Bioactive compounds
Biological properties
Cell death
Cell Line
Cell Line, Tumor
Cyclin D1
Cyclin D1 - metabolism
Diterpenes
Diterpenes - pharmacology
Drug development
Female
Fibroblasts - drug effects
Fibroblasts - metabolism
Gene expression
Glucosaminidase
Hep G2 Cells
Humanities and Social Sciences
Humans
Interleukin 10
MCF-7 Cells
Mice
Molecular modelling
multidisciplinary
Natural products
Necroptosis
Neovascularization, Pathologic - drug therapy
Neovascularization, Pathologic - metabolism
NF-kappa B - metabolism
NF-κB protein
Proto-Oncogene Proteins c-bcl-2 - metabolism
RelA gene
RelA protein
Science
Science (multidisciplinary)
Tumor cells
Tumor Necrosis Factor-alpha - metabolism
Tumor necrosis factor-α
Tumors
Vascular endothelial growth factor
Vascular Endothelial Growth Factor A - metabolism
ISSN:2045-2322, 2045-2322
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Zusammenfassung:Natural products have been recognized as important bioactive compounds on the basis of their wide biological properties. Here we investigated the antitumor effect and molecular mechanisms of the diterpene Fruticuline A (fruti) from Salvia lachnostachys , in human cancer cell lineages and Solid Ehrlich Carcinoma in mice. Fruti reduced MCF-7 and HepG2 proliferation by the reduction of Cyclin D1 levels and decreased NF-κB gene levels in both cell types. Furthermore, fruti also induced apoptosis in HepG2 cells, reduced Bcl-2 gene expression and induced necroptosis by increasing Ripk in MCF-7 cells. In mice, fruti prevented tumor development and reduced Cyclin D1, Bcl-2 and Rela gene levels, and reduced the p-NF-κB/NF-κB ratio in tumor tissue. Furthermore, fruti induced necrosis and apoptosis, increased N -acetyl-β-D-glucosaminidase and TNF-α levels and reduced IL-10 and Vegf levels in tumor tissue. Collectively, fruti exerts antitumor effects through the inhibition of the NF-κB pathway, reducing Cyclin D1 and Bcl-2 levels. In vitro the apoptosis and necroptosis pathways are involved in the cellular death, whereas in vivo , cells undergo necrosis by increased tumor inflammation and reduction of angiogenesis. Thus, fruticuline A acts in tumor cells by multiple mechanisms and represents a promising molecule for drug development in cancer treatment.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
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ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-020-73432-2