In vitro activity of aplidine, a new marine-derived anti-cancer compound, on freshly explanted clonogenic human tumour cells and haematopoietic precursor cells.
Aplidine is a new marine anti-cancer depsipeptide isolated from the Mediterranean tunicate Aplidium albicans. We have evaluated its antiproliferative action against a variety of freshly explanted human tumour specimens. Concentration ranges of 0.01-1.0 microM and 0.0001-1.0 microM were used in short- and long-term exposure schedules respectively. After exposure for 1 h in 49 evaluable specimens, aplidine showed a clear concentration-dependent anti-tumour effect. At 0.05 microM, 85% of the specimens were markedly inhibited. Continuous exposure for 21-28 days in 54 tumour specimens also led to a concentration-dependent activity relationship. Fifty per cent and 100% tumour inhibitions were achieved with 0.001 microM and 0.05 microM respectively. A head to head evaluation assessing short vs continuous exposure was carried out, resulting in evidence of an activity-time of exposure relationship. Breast, melanoma and non-small-cell lung cancer appear to be sensitive to low concentrations of aplidine. In addition the evaluation of the effects of aplidine on haematopoietic cells showed a concentration-dependent toxicity. However, under continuous exposure, active concentrations induced mild bone marrow toxicity, indicating that a therapeutic window at marginally myelotoxic concentrations might exist.
Depenbrock
H
H
Technische Universität München, Department of Medicine, Munich, Germany.
Peter
R
R
Faircloth
G T
GT
Manzanares
I
I
Jimeno
J
J
Hanauske
A R
AR
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D014410:Tumor Stem Cell Assay; D014561:Urochordata / Q000737:chemistry*
D000970:Antineoplastic Agents