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Planta Med 2021; 87(12/13): 1008-1017
DOI: 10.1055/a-1532-2384
Natural Product Chemistry and Analytical Studies
Original Papers

Cytotoxicity of Poupartone B, an Alkyl Cyclohexenone Derivative from Poupartia borbonica, against Human Cancer Cell Lines[ # ]

Allison Ledoux
1   Laboratory of Pharmacognosy, Center of Interdisciplinary Research on Medicines (CIRM), University of Liège, Belgium
,
Daphnée Bériot
2   Laboratory of Tumors and development Biology, GIGA-Cancer, CIRM, University of Liège, Liège, Belgium
,
Lucia Mamede
1   Laboratory of Pharmacognosy, Center of Interdisciplinary Research on Medicines (CIRM), University of Liège, Belgium
,
Pauline Desdemoustier
1   Laboratory of Pharmacognosy, Center of Interdisciplinary Research on Medicines (CIRM), University of Liège, Belgium
,
Fanny Detroz
1   Laboratory of Pharmacognosy, Center of Interdisciplinary Research on Medicines (CIRM), University of Liège, Belgium
,
Olivia Jansen
1   Laboratory of Pharmacognosy, Center of Interdisciplinary Research on Medicines (CIRM), University of Liège, Belgium
,
Michel Frédérich    *
1   Laboratory of Pharmacognosy, Center of Interdisciplinary Research on Medicines (CIRM), University of Liège, Belgium
,
Erik Maquoi   *
2   Laboratory of Tumors and development Biology, GIGA-Cancer, CIRM, University of Liège, Liège, Belgium
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Abstract

Poupartia borbonica is an endemic tree from the Mascarene Islands that belongs to the Anacardiaceae family. The leaves of this plant were phytochemically studied previously, and isolated alkyl cyclohexenone derivatives, poupartones A – C, demonstrated antiplasmodial and antimalarial activities. In addition to their high potency against the Plasmodium sp., high toxicity on human cells was also displayed. The present study aims to investigate in more detail the cytotoxicity and pharmacological interest of poupartone B, one of the most abundant derivatives in the leaves of P. borbonica. For that purpose, real-time live-cell imaging of different human cancer cell lines and normal fibroblasts, treated or not treated with poupartone B, was performed. A potent inhibition of cell proliferation associated with the induction of cell death was observed. A detailed morphological analysis of different adherent cell lines exposed to high concentrations of poupartone B (1 – 2 µg/mL) demonstrated that this compound induced an array of cellular alterations, including a rapid retraction of cellular protrusions associated with cell rounding, massive cytoplasmic vacuolization, loss of plasma membrane integrity, and plasma membrane bubbling, ultimately leading to paraptosis-like cell death. The structure-activity relation of this class of compounds, their selective toxicity, and pharmacological potential are discussed.

Key words

Anacardiaceae - Poupartia borbonica - poupartone B - cancer - cytotoxicity - live-cell imaging

# Dedicated to Professor Arnold Vlietinck on the occasion of his 80th birthday.


* MF and EM are co-senior authors of this work.


Supporting Information

    MDA-MB-231 cells were treated with increasing concentrations of poupartone B (0.5 – 2 µg/mL) or vehicle only. Phase-contrast time-lapse images of the different culture conditions after 0, 6, 12, 24, 36, and 48 h of treatment are illustrated in Fig. 1S (Supporting Information). A2058 cells were treated with increasing concentrations of poupartone B (0.5 – 2 µg/mL) or vehicle only. Phase-contrast time-lapse images of the different culture conditions after 0, 6, 12, 24, 36, and 48 h of treatment are illustrated in Fig. 2S (Supporting Information). A375 cells were treated with increasing concentrations of poupartone B (0.5 – 2 µg/mL) or vehicle only. Phase-contrast time-lapse images of the different culture conditions after 0, 6, 12, 24, 36, and 48 h of treatment are illustrated in Fig. 3S (Supporting Information). Fibroblasts were treated with increasing concentrations of poupartone B (0.5 – 2 µg/mL) or vehicle only. Phase-contrast time-lapse images of the different culture conditions after 0, 6, 12, 24, 36, and 48 h of treatment are illustrated in Fig. 4S (Supporting Information).

    MDA-MB-231, A2058, A375, normal fibroblasts, HL-60, and OCI-LY19 cells were treated with increasing concentrations (0 – 2 µg/mL) of poupartone B, and live-cell imaging was used to measure the relative cell confluency. The areas under the relative cell confluency versus time curves (AUC) are plotted for each concentration tested. Dose-response curves (gray curves) were fitted using the inhibitory concentration versus response–variable slope (4 parameters) function of Graphpad Prism. A representative experiment is illustrated in Fig. 5S (Supporting Information).

    MDA-MB-231 cells were exposed to poupartone B (1 µg/mL), and time-lapse imaging by holo-tomographic microscopy was performed for 13 h; the video is available as Supporting Information.

  • Supporting Information


Publication History

Received: 15 January 2021

Accepted after revision: 14 June 2021

Article published online:
16 July 2021

© 2021. Thieme. All rights reserved.

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