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Palmatine from Unexplored Rutidea parviflora Showed Cytotoxicity and Induction of Apoptosis in Human Ovarian Cancer Cells

1
Guy Hilton Research Centre, School of Pharmacy and Bioengineering, Keele University, Stoke-on-Trent ST4 7QB, UK
2
Faculty of Pharmaceutical Sciences, University of Port Harcourt, Port Harcourt, PMB 5323, Nigeria
*
Author to whom correspondence should be addressed.
Part of this study was presented at the 5th International Conference on the Mechanism of Action of Nutraceuticals, Aberdeen, UK.
Toxins 2019, 11(4), 237; https://doi.org/10.3390/toxins11040237
Received: 21 March 2019 / Revised: 17 April 2019 / Accepted: 18 April 2019 / Published: 25 April 2019
(This article belongs to the Special Issue Biological Activities of Alkaloids: From Toxicology to Pharmacology)
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Abstract

Ovarian cancer ranks amongst the deadliest cancers in the gynaecological category of cancers. This research work aims to evaluate in vitro anti-ovarian cancer activities and identify phytochemical constituents of a rarely explored plant species—Rutidea parviflora DC. The aqueous and organic extracts of the plant were evaluated for cytotoxicity using sulforhodamine B assay in four ovarian cancer cell lines and an immortalized human ovarian epithelial (HOE) cell line. The bioactive compounds were isolated and characterized by gas/liquid chromatography mass spectrometry and nuclear magnetic resonance spectroscopy. Caspase 3/7 activity assay, western blotting and flow cytometry were carried out to assess apoptotic effects of active compounds. The extracts/fractions of R. parviflora showed promising anti-ovarian cancer activities in ovarian cancer cell lines. A principal cytotoxic alkaloid was identified as palmatine whose IC50 was determined as 5.5–7.9 µM. Palmatine was relatively selective towards cancer cells as it was less cytotoxic toward HOE cells, also demonstrating interestingly absence of cross-resistance in cisplatin-resistant A2780 cells. Palmatine further induced apoptosis by increasing caspase 3/7 activity, poly-ADP-ribose polymerase cleavage, and annexin V and propidium iodide staining in OVCAR-4 cancer cells. Our studies warranted further investigation of palmatine and R. parviflora extracts in preclinical models of ovarian cancer. View Full-Text
Keywords: Ovarian cancer; Rutidea parviflora; Palmatine; Apoptosis Ovarian cancer; Rutidea parviflora; Palmatine; Apoptosis
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Johnson-Ajinwo, O.R.; Richardson, A.; Li, W.-W. Palmatine from Unexplored Rutidea parviflora Showed Cytotoxicity and Induction of Apoptosis in Human Ovarian Cancer Cells. Toxins 2019, 11, 237.

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