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CC BY-NC-ND 4.0 · Planta Medica International Open 2020; 7(01): e1-e11
DOI: 10.1055/a-1063-6722
Original Papers
Eigentümer und Copyright ©Georg Thieme Verlag KG 2020

Inhibition of HIF-1α through Suppression of NF-κB Activation by Compounds Isolated from Senecio graveolens

Luis Apaza Ticona 
1   Department of Organic Chemistry, Faculty of Sciences, University Autónoma of Madrid, Cantoblanco, Madrid, Spain
2   Department of Pharmacology, Pharmacognosy and Botany, Faculty of Pharmacy, University Complutense of Madrid, Madrid, Spain
,
Nuria Cano-Adamuz
1   Department of Organic Chemistry, Faculty of Sciences, University Autónoma of Madrid, Cantoblanco, Madrid, Spain
,
Andreea Madalina Serban
3   Maria Sklodowska Curie University Hospital for Children, Bucharest, Romania
,
Ángel Rumbero Sánchez
1   Department of Organic Chemistry, Faculty of Sciences, University Autónoma of Madrid, Cantoblanco, Madrid, Spain
› Author Affiliations Acknowledgments This work was supported by the National Herbarium of Bolivia, the Fundación de la Universidad Autónoma de Madrid (FUAM).
Further Information

Publication History

received 17 June 2019
revised 16 November 2019

accepted 18 November 2019

Publication Date:
20 January 2020 (online)

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Abstract

One of the characteristics of cancer is that the lack of oxygen in the cancer cells triggers changes in their gene expression. This hypoxia activates hypoxia-inducible factor 1-alpha and this in turn sets in motion the whole family of important angiogenic genes for the tumour. Hypoxia-inducible factor 1-alpha therefore increases the density and vascular permeability within the tumours, facilitating their rapid growth and, later, the metastasis. Senecio graveolens is a South American medicinal plant commonly used for mountain sickness (lack of adaptation of the organism to hypoxia). Additionally, pharmacological studies showed that its alcoholic extracts have cytotoxic properties.

This research aimed to perform a guided phytochemical study of S. graveolens to identify compounds capable of inhibiting hypoxia-inducible factor 1-alpha through suppression of nuclear factor kappa-light-chain-enhancer of activated B cell activation. The isolation led to the characterisation of phanurane (1), damsine (2), and scoparone (3), first reported in the S. graveolens species.

Phanurane (1 ) showed inhibitory activity of hypoxia-inducible factor 1-alpha on the cancer cell lines U-373 MG (IC50=20.66±0.04 μM), A549 (IC50=25.80±0.04 μM), Hep G2 (IC50=29.21±0.03 μM), and Caco-2 (IC50=38.58±0.02 μM). Damsine (2) hypoxia-inducible factor 1-alpha displayed inhibitory activity of hypoxia-inducible factor 1-alpha on the cancer cell lines U-373 MG (IC50=2.29±0.07 μM), A549 (IC50=4.13±0.04 μM), Hep G2 (IC50=6.40±0.03 μM), and Caco-2 (IC50=9.80±0.04 μM). Finally, scoparone (3) displayed inhibitory activity of hypoxia-inducible factor 1-alpha on the cancer cell lines U-373 MG (IC50=15.22±0.01 μM), A549 (IC50=17.47±0.02 μM), Hep G2 (IC50=18.26±0.06 μM), and Caco-2 (IC50=19.75±0.04 μM).

In addition, phanurane (1 ) displayed inhibitory activity over nuclear factor kappa-light-chain-enhancer of activated B cells on cancer cell lines U-373 MG (IC50=7.13±0.03 μM), A549 (IC50=8.64±0.03 μM), Hep G2 (IC50=8.87±0.04 μM), and Caco-2 (IC50=15.11±0.01 μM). Likewise, damsine (2) showed inhibitory activity over nuclear factor kappa-light-chain-enhancer of activated B cells on cancer cell lines U-373 MG (IC50=2.28±0.01 μM), A549 (IC50=3.79±0.02 μM), Hep G2 (IC50=3.98±0.05 μM), and Caco-2 (IC50=6.41±0.02 μM). Lastly, scoparone (3) displayed inhibitory activity of nuclear factor kappa-light-chain-enhancer of activated B cells on cancer cell lines U-373 MG (IC50=3.62±0.06 μM), A549 (IC50=4.48±0.03 μM), Hep G2 (IC50=5.25±0.01 μM), and Caco-2 (IC50=11.90±0.02 μM).

This study corroborates the cytotoxic activity of the isolated compounds through the inhibition of hypoxia-inducible factor 1-alpha as well as its modulator nuclear factor kappa-light-chain-enhancer of activated B cells.

Key words

coumarins - sesquiterpene lactones - Senecio graveolens - Asteraceae - NF-κB - HIF-1α

Supplementary Material

    Supplementary Material for this article is available online at http://www.thieme-connect.de/products.
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