Characterization of the cytotoxic activity of the indoloquinoline alkaloid cryptolepine in human tumour cell lines and primary cultures of tumour cells from patients |
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Authors: | Daniel Laryea Anders Isaksson Colin W Wright Rolf Larsson Peter Nygren |
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Institution: | (1) Division of Clinical Pharmacology, Department of Medical Sciences, University Hospital, 751 85 Uppsala, Sweden;(2) Bradford School of Pharmacy, University of Bradford, Bradford, West Yorkshire, BD7 1DP, UK;(3) Division of Oncology, Department of Oncology, Radiology and Clinical Immunology, University Hospital, 751 85 Uppsala, Sweden |
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Abstract: | The plant derived indoloquinoline alkaloid cryptolepine was investigated for its cytotoxic properties in 12 human tumour cell
lines and in primary cultures of tumour cells from patients. The fluorometric microculture cytotoxicity assay was used to
assess cytotoxicity and DNA micro-array analysis to evaluate gene expression. Cryptolepine mean IC50 in the cell line panel was 0.9 μM compared with 1.0 and 2.8 μM in haematological and solid tumour malignancies, respectively.
Among patient solid tumour samples, those from breast cancer were the most sensitive and essentially as sensitive as haematological
malignancies. Cryptolepine activity showed highest correlations to topoisomerase II and microtubule targeting drugs. In the
cell lines cryptolepine activity was essentially unaffected by established mechanisms of drug resistance. A number of genes
were identified as associated with cryptolepine activity. In conclusion, cryptolepine shows interesting in vitro cytotoxic
properties and its further evaluation as an anti-cancer drug seems warranted. |
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