(+)-
Ptilocaulin, a novel cyclic
guanidine extracted from the Caribbean sponge Ptilocaulis aff. P. Spiculifer, is reported to have broad spectrum antimicrobial activity in vitro as well as in vitro activity against L1210 murine
leukemia. To more fully evaluate this compound as an
anticancer agent, the in vitro cell growth inhibitory potencies of synthetic racemic
ptilocaulin and ten clinical anticancer drugs were determined and compared in 16 different normal and transformed human and murine cell populations. Potency, expressed as the 50% inhibitory concentration (IC50), was determined by a tetrazolium reduction (MTT) assay.
Ptilocaulin showed a fairly broad spectrum of in vitro activity against colon and mammary
adenocarcinomas,
melanomas,
leukemias, transformed fibroblasts and normal lymphoid cells (IC50s 0.05- greater than 10 micrograms/ml). This activity was comparable to that of many of the clinical drugs, including vinca alkyloids,
antibiotics,
alkylators and
antimetabolites. Cell viability was affected only after a 72 hr exposure to the compound. In a clonogenic assay, cytocidal effects were observed after 24-72 hr exposures to 10 x IC50 concentrations of
ptilocaulin, as evidenced by failure of cells to resume growth after removal of the compound.
Cytostatic effects were observed at less than or equal to IC50 concentrations, as evidenced by resumption of growth to near-control levels after removal of the compound.
Ptilocaulin was toxic at 50 and 25 mg/kg in an in vivo L1210
tumor model and was ineffective at lower concentrations (T/Cs 100-112%). In vivo studies in a more sensitive
tumor system are recommended but are limited by the lack of availability of sufficient quantities of the compound.