In vitro interaction between ecteinascidin 743 (ET-743) and radiation, in relation to its cell cycle effects.
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 > or =1.8 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.
Simoens
C
C
Laboratory of Cancer Research and Clinical Oncology, Department of Medical Oncology, University of Antwerp (UIA/UZA), Universiteitsplein 1, B-2610 Wilrijk, Antwerp, Belgium. cindy.simoens@ua.ac.be
Korst
A E C
AE
De Pooter
C M J
CM
Lambrechts
H A J
HA
Pattyn
G G O
GG
Faircloth
G T
GT
Lardon
F
F
Vermorken
J B
JB
D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D002277:Carcinoma / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D002453:Cell Cycle / Q000187:drug effects* / Q000528:radiation effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D003131:Combined Modality Therapy; D004149:Dioxoles / Q000494:pharmacology*; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D044005:Tetrahydroisoquinolines; D014062:Tongue Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy; D000077606:Trabectedin; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy
D018906:Antineoplastic Agents, Alkylating; D004149:Dioxoles; D007546:Isoquinolines; D011838:Radiation-Sensitizing Agents; D044005:Tetrahydroisoquinolines; D000077606:Trabectedin