Issue 70, 2017, Issue in Progress
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RSC Advances

Isochondodendrine and 2′-norcocsuline: additional alkaloids from Triclisia subcordata induce cytotoxicity and apoptosis in ovarian cancer cell lines†‡

Fidelia Ijeoma Uche, ORCID logo ab   Mohammed N. Abed,a   Marwan I. Abdullah,a   Falko P. Drijfhout,c   James McCullagh,d   Timothy W. D. Claridge, ORCID logo d   Alan Richardsona  and  Wen-Wu Li ORCID logo *a  

* Corresponding authors

a Institute for Science and Technology in Medicine, Keele University, Stoke-on-Trent, UK
E-mail: w.li@keele.ac.uk
Tel: +44 (0)1782 674382

b Faculty of Pharmaceutical Sciences, University of Port Harcourt, Nigeria

c Chemical Sciences Research Centre, Keele University, Staffordshire, UK

d Chemical Research Laboratory, University of Oxford, Oxford, UK

Abstract

Triclisia subcordata Oliv (Menispermeaceae) is used in herbal medicine for the treatment of cancer and other diseases in Africa. This study aims to isolate minor alkaloids present in this plant and assay their cytotoxic activities. Isochondodendrine and 2′-norcocsuline as two minor alkaloids together with the abundant cycleanine were isolated and identified by mass spectrometry and NMR spectroscopy. Both isochondodendrine and 2′-norcocsuline exhibited in vitro cytotoxicity in four ovarian cancer cell lines (A2780, IGROV-1, OVCAR-8, and OVCAR-4) with IC50 ranges of 3.5–17 μM and 0.8–6.2 μM respectively. These alkaloids showed mostly slightly weaker potencies when tested using normal human ovarian epithelial cells, IC50 = 10.5 ± 1.2 μM and 8.0 ± 0.2 μM for isochondodendrine and 2′-norcocsuline, respectively. The alkaloids induced apoptosis in ovarian cancer cells because they activated caspases 3/7, induced cleavage of PARP, increased the subG1 population in cell cycle analysis and increased Annexin V/propidium iodide staining. These observations suggest that isochondodendrine and 2′-norcocsuline contributing to the cytotoxic activity of T. subcordata may be suitable starting points for the future development of novel therapeutics to treat ovarian cancer.

Graphical abstract: Isochondodendrine and 2′-norcocsuline: additional alkaloids from Triclisia subcordata induce cytotoxicity and apoptosis in ovarian cancer cell lines

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Article information

DOI
https://doi.org/10.1039/C7RA08032H
Article type
Paper
Submitted
20 Jul 2017
Accepted
05 Sep 2017
First published
12 Sep 2017
This article is Open Access
Creative Commons BY-NC license

RSC Adv., 2017,7, 44154-44161

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Isochondodendrine and 2′-norcocsuline: additional alkaloids from Triclisia subcordata induce cytotoxicity and apoptosis in ovarian cancer cell lines

F. I. Uche, M. N. Abed, M. I. Abdullah, F. P. Drijfhout, J. McCullagh, T. W. D. Claridge, A. Richardson and W. Li, RSC Adv., 2017, 7, 44154 DOI: 10.1039/C7RA08032H

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