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Toxicological Sciences 70, 245-251 (2002)
Copyright © 2002 by the Society of Toxicology

SAFETY EVALUATION

The Popular Herbal Antimalarial, Extract of Cryptolepis sanguinolenta, Is Potently Cytotoxic

Charles Ansah and Nigel J. Gooderham1

Molecular Toxicology, Faculty of Medicine, Sir Alexander Fleming Building, Imperial College of Science, Technology and Medicine, Exhibition Road, London, SW7 2AZ, UK

The aqueous root extract of Cryptolepis sanguinolenta (CSE) is a popular antimalarial in West African ethnomedicine. Cryptolepine (CLP), the major alkaloid of the plant, is a cytotoxic DNA intercalator that has promise as an anticancer agent. To date the aqueous root extract, the traditional antimalarial formulation, has not been evaluated for toxicity. In this study, we have examined the in vitro toxicity of CSE and CLP using V79 cells, a Chinese hamster lung fibroblast frequently used to assess genetic toxicity, and a number of organ-specific human cancer cell lines. CSE and CLP caused a dose- and time-dependent reduction in viability of the V79 cell line. Flow cytometric analysis of CSE- and CLP-treated (24 h) asynchronously growing V79 cells using propidium iodide (PI) staining revealed an accumulation of cells (up to 55%) in the sub-G1 phase of the cell cycle, indicative of cell death. The V79 cells and almost all the organ-specific human cancer cell lines exposed to CSE and CLP were profoundly growth inhibited, as measured in a clonogenicity assay. In a V79 cell mutation assay ( hprt gene), CSE (5–50 µg/ml) only induced mutation at the highest dose employed (mutation frequency ~4 and 38 mutant clones per 10 6cells for control and CSE, respectively), but CLP (0.5–5.0 µM) was not mutagenic. These results indicate that CSE and CLP are very cytotoxic and may be weak mammalian mutagens and/or clastogens. The poor genotoxicity of CSE and CLP coupled with their potent cytotoxic action support their anticancer potential.

Key Words: Cryptolepis sanguinolenta; cryptolepine; cytotoxicity; hprt mutation; alamar blue; Trypan blue; clonogenicity.


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H. Zhu and N. J. Gooderham
Mechanisms of Induction of Cell Cycle Arrest and Cell Death by Cryptolepine in Human Lung Adenocarcinoma A549 Cells
Toxicol. Sci., May 1, 2006; 91(1): 132 - 139.
[Abstract] [Full Text] [PDF]


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