Planta Med 2022; 88(15): 1534
DOI: 10.1055/s-0042-1759244
Poster Session II

Cytotoxic activities of 15-hydroxyangustilobine A, a major indole alkaloid from the leaves of Alstonia boonei

R Börner
University of Münster, Institute for Pharmaceutical Biology and Phytochemistry, Münster, Germany
,
M Grimm
University of Münster, Institute for Pharmaceutical Biology and Phytochemistry, Münster, Germany
,
L Greiffer
University of Münster, Institute for Pharmaceutical Biology and Phytochemistry, Münster, Germany
,
J Jacobtorweihen
University of Münster, Institute for Pharmaceutical Biology and Phytochemistry, Münster, Germany
,
V Spiegler
University of Münster, Institute for Pharmaceutical Biology and Phytochemistry, Münster, Germany
› Author Affiliations
 

Alstonia boonei De Wild. is a medicinal plant traditionally used in West Africa for treatment of various ailments. The composition of the bark has been frequently investigated due to its popular use against malaria [1], however, not much is known about the phytochemistry of the leaves [2], although they are prepared as decoctions to treat different types of cancer in Ghana [3].

The cytotoxic activity of a hydroethanolic leaf extract was therefore assessed in a panel of ten cell lines (A549, MCF-7, MDA-MB- 231, A431, LNCap, RD-ES, CADO-ES-1, REH, HL-60 and Vero) by MTT assay including doxorubicin as positive control (IC50 0.02 – 13.4 µM). The cell viability was reduced in all cell lines (IC50 22.8 – 73.1 µg/mL) and a subsequent bioassay-guided fractionation revealed 15-hydroxyangustilobine A (15-HA) as the only compound significantly affecting cell viability (IC50 15.5 – 72.9 µM; MCF-7, RD-ES, CADO-ES-1, REH, HL-60, CCRF-CEM and Vero). Additionally, 15-HA led to apoptosis and cell cycle arrest at G2/M phase, determined by flow cytometry. Fluorescence microscopy and assessment of topoisomerase I activity indicated a mode of action distinct from other natural product derived anticancer drugs, e.g. vincristine, camptothecin or paclitaxel. Further indole alkaloids representing major phytochemical constituents of the extract, namely alstrostines C – E, 12-methoxyechitamidine, 19-oxo-12-methoxyechitamidine, 6,7-seco-angustilobine B and 6,7-seco-19,20-α-epoxyangustilobine B, were isolated, but did not contribute to the bioactivity.

In summary, the current study identified the major indole alkaloids that were previously unreported in A. boonei leaves and revealed 15-HA as the active component causing moderate cytotoxicity in selected cell lines.



Publication History

Article published online:
12 December 2022

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