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Updated: Aug 15, 2026
Establishing 3-Dimensional Spheroids from Patient-Derived Tumor Samples and Evaluating their Sensitivity to Drugs
Published on: December 16, 2022
Cytotoxicity of sphingoid marine compound analogs in mono- and multilayered solid tumor cell cultures
José M Padrón1, Godefridus J Peters
1Department of Medical Oncology, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands. jmpadron@ull.es
Abstract:
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 microM. 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 microM. 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)/G1 at a low drug concentration (3 microM) but accumulation in S phase at a high drug concentration (9 microM). 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.
Insights
Four synthetic marine sphingoid analogs showed anticancer potential against various human tumor cell lines. Compounds 5 and 8 demonstrated significant activity, particularly in three-dimensional cell cultures, suggesting potential for novel cancer therapies.
Area of Science:
- Marine natural products chemistry
- Cancer biology
- Drug discovery
Background:
- Sphingoid marine compounds are a class of molecules with potential biological activity.
- Preliminary in vitro studies identified promising cytotoxic effects of certain synthetic analogs.
Purpose of the Study:
- To further analyze a subset of four synthetic sphingoid marine compound analogs.
- To evaluate their anticancer potential against a panel of human tumor cell lines using different culture models.
Main Methods:
- Initial screening in monolayer cultures against eight human tumor cell lines (ovarian, colon, lung, squamous cell carcinoma, leukemia).
- Secondary screening in multilayered, postconfluent cultures of A2780 ovarian and WiDr colon cancer cells.
- Cell cycle analysis in HL60 leukemia cells.
Main Results:
- Compounds exhibited IC50 values from 1.5 to 6.9 microM in monolayer cultures.
- Compounds 5 and 8 were most active in multilayered cultures with EC50 values of 25-32 microM.
- Cell cycle arrest observed in G(0)/G1 at low concentrations and S phase accumulation at high concentrations in HL60 cells.
Conclusions:
- The synthetic sphingoid analogs display cell line-independent activity.
- Compounds 5 and 8 show selectivity for cells in three-dimensional culture models, mimicking physiological conditions.
- These analogs represent potential candidates for novel anticancer drug development, outperforming standard drugs in certain models.
