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Cytotoxicity of sphingoid marine compound analogs in mono- and multilayered solid tumor cell cultures

  • José M. PadrónEmail author
  • Godefridus J. Peters
Preclinical Studies

Summary

A subset of four synthetic sphingoid marine compound analogs was chosen from a preliminary in vitro cytotoxicity study for further analysis. The selected analogs were initially screened in monolayer cultures for their anticancer potential against a panel of eight human tumor cell lines, ovarian, colon and lung cancer, squamous cell carcinoma and leukemia producing IC50 values ranging from 1.5 to 6.9 μM. In a secondary screening, the sphingoid analogs were evaluated against multilayered postconfluent cultures of A2780 ovarian cancer and WiDr colon cancer cells. In this model, compounds 5 and 8 were the most active derivatives showing EC50 values in the range 25–32 μM. The performance of 5 and 8 against both cell lines was not dependent on the cell culture model as shown with resistance factor values in the range 8–12. Cell cycle studies in HL60 leukemia cells showed an arrest in G 0/G 1 at a low drug concentration (3 μM) but accumulation in S phase at a high drug concentration (9 μM). It can be concluded that the analogs showed a cell line independent activity, with an apparent selectivity against cells grown in more physiological three-dimensional condition compared to standard anticancer drugs.

Key Words

sphingosine sphinganine spisulosine pachastrissamine solid tumor multilayered postconfluent cultures 

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Copyright information

© Springer Science + Business Media, LLC 2005

Authors and Affiliations

  1. 1.Instituto Canario de Investigación del CáncerUnidad de Investigación, Hospital Univ. NS de CandelariaS/C de TenerifeSpain
  2. 2.Department of Medical OncologyVU University Medical Center, De Boelelaan 1117, 1081 HVAmsterdamThe Netherlands
  3. 3.Instituto Canario de Investigación del Cáncer (ICIC)Red Temática de Investigación Cooperativa de Centros de Cáncer (RTICCC)S/C de TenerifeSpain

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