Characterization of the cytotoxic activity of the indoloquinoline alkaloid cryptolepine in human tumour cell lines and primary cultures of tumour cells from patients
2009 (English)In: Investigational new drugs, ISSN 0167-6997, E-ISSN 1573-0646, Vol. 27, no 5, 402-411 p.Article in journal (Refereed) Published
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 IC(50) in the cell line panel was 0.9 muM compared with 1.0 and 2.8 muM 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.
Place, publisher, year, edition, pages
2009. Vol. 27, no 5, 402-411 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-102563DOI: 10.1007/s10637-008-9185-5ISI: 000269884100002PubMedID: 18853102OAI: oai:DiVA.org:uu-102563DiVA: diva2:216382