In vitro interaction between Ecteinascidin 743 (ET-743) and radiation, in relation to its cell cycle effects
Simoens, C.; Korst, A.E.C.; De Pooter, C.M.J.; Lambrechts, H.A.J.; Pattyn, G.G.O.; Faircloth, G.T.; Lardon, F.; Vermorken, J.B. (2003). In vitro interaction between Ecteinascidin 743 (ET-743) and radiation, in relation to its cell cycle effects. British Journal of Cancer 89(12): 2305-2311. https://hdl.handle.net/10.1038/sj.bjc.6601431
In: British Journal of Cancer. Nature Publishing Group: London. ISSN 0007-0920; e-ISSN 1532-1827, more
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| Author keywords |
ET-743; radiation; radiosensitisation; cell cycle |
| Authors | | Top |
- Simoens, C.
- Korst, A.E.C.
- De Pooter, C.M.J.
- Lambrechts, H.A.J.
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- Pattyn, G.G.O.
- Faircloth, G.T.
- Lardon, F.
- Vermorken, J.B.
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| Abstract |
Ecteinascidin 743 (ET-743) is a new marine-derived agent with promising activity against a number of solid tumours. In four human tumour cell lines, the interaction between ET-743 and radiation was investigated in relation to the effects of ET-743 on the cell cycle, in vitro. Cell survival was measured based on quantitative staining of cellular protein by sulforhodamine B. A 24 h treatment with ET-743 before radiation resulted in a moderate increase in radiosensitivity in three out of four cell lines. Dose enhancement factors greater than or equal to1.8 were observed for concentrations resulting in 52, 46 and 30% cell kill in ECV304, H292 and CAL-27, respectively, whereas in A549 no radiosensitisation was observed (no significant increase in radiosensitivity). According to the combination index analysis, synergism was observed only in ECV304 and CAL-27 cells. A 24 h incubation with ET-743 resulted in a concentration-dependent G2/M block, which might explain the moderate radiosensitising effects in ECV304 and H292. The lack of radiosensitisation in A549 might be due to the S phase delay preceding the G2/M block at the moment of radiation, which only occurred in this cell line. In conclusion, ET-743 has moderate cell line-dependent radiosensitising properties; however, only when cytotoxic concentrations of ET-743 are used. In one of the four cell lines tested, no radiosensitisation was observed. |
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