Bufadienolides from Helleborus foetidus and their cytotoxic properties on MCF-7 breast cancer cells

Olivier Potterat; Marina Kaufmann; Cécile Tschopp; Michaela Caj; Jakob K Reinhardt; Alessandro Prescimone; Devika Shah; Stephan Baumgartner; Michel-Angelo Sciotti; Laura Suter-Dick

doi:10.1016/j.phytochem.2024.114329

Bufadienolides from Helleborus foetidus and their cytotoxic properties on MCF-7 breast cancer cells

Phytochemistry. 2024 Nov 15:230:114329. doi: 10.1016/j.phytochem.2024.114329. Online ahead of print.

Affiliations

¹ Division of Pharmaceutical Biology, University of Basel, Klingelbergstrasse 50, CH-4056, Basel, Switzerland. Electronic address: olivier.potterat@unibas.ch.
² Division of Pharmaceutical Biology, University of Basel, Klingelbergstrasse 50, CH-4056, Basel, Switzerland.
³ Institute for Chemistry and Bioanalytics, School of Life Sciences, University of Applied Sciences and Arts Northwestern Switzerland, Hofackerstrasse 30, CH-4132, Muttenz, Switzerland.
⁴ University of Basel, Department of Chemistry, Mattenstrasse 22, CH-4058, Basel, Switzerland.
⁵ Iscador AG, Kirschweg 9, CH-4144, Arlesheim, Switzerland; Association for Cancer Research, Hiscia Institute, Kirschweg 9, CH-4144, Arlesheim, Switzerland.
⁶ Association for Cancer Research, Hiscia Institute, Kirschweg 9, CH-4144, Arlesheim, Switzerland; Institute for Integrative Medicine, University of Witten/Herdecke, Gerhard-Kienle-Weg 4, D-58313, Herdecke, Germany.

PMID: 39549941
DOI: 10.1016/j.phytochem.2024.114329

Abstract

Twelve bufadienolides and six 19-norbufadienolides were isolated from the aerial parts of Helleborus foetidus. They consist of aglycons and glucosides and include nine previously undescribed compounds and a compound reported for the first time as a genuine natural product. Their structures were established by extensive spectroscopic analysis and the structure and absolute configuration of two previously unreported 3,4-epoxy derivatives were confirmed by single crystal X-ray diffraction analysis. The compounds were tested for their cytotoxicity on MCF-7 human breast cancer cells. They show differential cytotoxic activity with IC₅₀ values in the range of 2.4 nM - >10 μM. The potency of the activity strongly correlates with the presence of a C-19 aldehyde group. The data complement the scientific basis underpinning the use of H. foetidus in anthroposophic medicine for the integrative treatment of cancer.

Keywords: Bufadienolides; Cytotoxicity; Helleborus foetidus; MCF-7 cells; Ranunculaceae.