Sequence-dependent enhancement of cytotoxicity produced by ecteinascidin 743 (ET-743) with doxorubicin or paclitaxel in soft tissue sarcoma cells Journal Article


Authors: Takahashi, N.; Li, W.; Banerjee, D.; Scotto, K. W.; Bertino, J. R.
Article Title: Sequence-dependent enhancement of cytotoxicity produced by ecteinascidin 743 (ET-743) with doxorubicin or paclitaxel in soft tissue sarcoma cells
Abstract: Ecteinascidin 743 (ET-743) is a potent antitumor agent from the Caribbean tunicate Ecteinascidin turbinata and is presently in clinical trials for human cancers. To better understand how ET-743 might be used clinically, the present study used SRB assays to examine the cytotoxicity resulting from combining ET-743 with three other antineoplastic agents: doxorubicin (DXR), trimetrexate, and paclitaxel in different administration schedules in two soft tissue sarcoma cell lines, HT-1080 and HS-18, in vitro. Concurrent exposure of ET-743 with DXR resulted in synergistic interactions in both cell lines. Addition of ET-743 for 24 h before DXR was the most effective cytotoxic regimen against both cell lines. Morphological study by fluorescence microscopy revealed that combination treatment of both cells with ET-743 and DXR induced apoptosis. Exposure to paclitaxel before ET-743 was also an effective regimen. These results encourage studies of the combination of ET-743 and DXR in the treatment of soft tissue sarcoma, because each of these agents have activity in this disease.
Keywords: controlled study; human cell; doxorubicin; drug potentiation; antineoplastic agents; paclitaxel; flow cytometry; cell division; apoptosis; drug potency; tumor cells, cultured; sarcoma; drug synergism; soft tissue sarcoma; fluorescence microscopy; microscopy, fluorescence; drug cytotoxicity; trabectedin; inhibitory concentration 50; dioxoles; isoquinolines; trimetrexate; tetrahydroisoquinolines; humans; human; priority journal; article
Journal Title: Clinical Cancer Research
Volume: 7
Issue: 10
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2001-10-01
Start Page: 3251
End Page: 3257
Language: English
PUBMED: 11595721
PROVIDER: scopus
DOI/URL:
Notes: Export Date: 21 May 2015 -- Source: Scopus
Citation Impact
MSK Authors
  1. Weiwei Li
    63 Li
  2. Debabrata Banerjee
    136 Banerjee
  3. Kathleen Weihs Scotto
    56 Scotto
  4. Joseph Bertino
    363 Bertino