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Journal of Biomolecular Screening
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Selective Cytotoxicity Evaluation in Anticancer Drug Screening of Fractionated Plant Extracts

Petra Lindholm

Division of Pharmacognosy, Department of Medicinal Chemistry, Biomedical Centre, Uppsala University, Uppsala, Sweden

Joachim Gullbo

Division of Clinical Pharmacology, Department of Medical Sciences, Uppsala Academic Hospital, Uppsala, Sweden

Per Claeson

Division of Pharmacognosy, Department of Medicinal Chemistry, Biomedical Centre, Uppsala University, Uppsala, Sweden

Ulf Goransson

Division of Pharmacognosy, Department of Medicinal Chemistry, Biomedical Centre, Uppsala University, Uppsala, Sweden

Senia Johansson

Division of Pharmacognosy, Department of Medicinal Chemistry, Biomedical Centre, Uppsala University, Uppsala, Sweden

Anders Backlund

Division of Pharmacognosy, Department of Medicinal Chemistry, Biomedical Centre, Uppsala University, Uppsala, Sweden

Rolf Larsson

Division of Clinical Pharmacology, Department of Medical Sciences, Uppsala Academic Hospital, Uppsala, Sweden

Lars Bohlin

Division of Pharmacognosy, Department of Medicinal Chemistry, Biomedical Centre, Uppsala University, Uppsala, Sweden

Chosen to reflect biodiversity in a phylogenetic sense, 100 fractionated plant extracts were screened in vitro for cytotoxicity following extraction and fractionation (polypeptide isolation). Of these 100 extracts, 30 were selected and then characterized preliminarily for antitumor potency and mode of action by testing them on two cell lines and primary cultures of human tumor cells. On the basis of cytotoxicity potency, 10 of the extracts were further characterized for anticancer activity in 10 human tumor cell lines. This final testing resulted in seven potential lead plants with superior evidence of antitumor potential: Colchicum autumnale L. (Colchicaceae), Digitalis lanata Ehrh. and Digitalis purpurea L. (Plantaginaceae), Helleborus cyclophyllus Boiss. (Ranunculaceae), Menyanthes trifoliata L. (Menyanthaceae), and Viola arvensis Murr. and Viola patrinii Ging. (Violaceae). Within a database of antitumor compounds, the activity profiles of the extracts from these seven plants were compared, by correlation analysis, with those of more than 100 other compounds, including 39 standard drugs from different classes of cytotoxic mechanisms. The activity profiles of six of these candidates were uncorrelated with those of the standard drugs, possibly indicating new pathways of drug-mediated cell death.

Journal of Biomolecular Screening, Vol. 7, No. 4, 333-340 (2002)
DOI: 10.1177/108705710200700405
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