The effect of Senecio latifolius a plant used as a South African traditional medicine, on a human hepatoma cell line

A number of traditional remedies used in South Africa contain pyrrolizidine alkaloids, some of which are hepatotoxic. We investigated the effect on hu man HuH-7 cells of Senecio latifolius DC., a plant that is a component of s ome traditional remedies and which is known to contain toxic pyrrolizidine alkaloids. Cells were also treated with extracts of a standard pyrrolizidin e, retrorsine. The changes in the gross morphology of the cells were studie d using light microscopy after haematoxylin and eosin staining. The cytoske leton was investigated using fluorescence-labelled anti-p-tubulin antibody and the nuclear organisation was studied using fluorescence-labelled antinu clear antibodies. The plant extracts gave rise to dose-dependent gross morp hological changes. At high doses, we observed necrosis and at lower doses, destruction of the cytoskeleton, nuclear fragmentation and apoptosis. Doses of less than the equivalent of 330 ng/ml retrorsine led to multinucleated cells with failure in spindle formation and clumping of nuclear chromatin. This latter finding suggests that chronic low-dose treatment with such trad itional remedies could give rise to teratogenic and/or carcinogenic effects . (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.