Enhanced antitumor activity of irofulven in combination with 5-fluorouracil and cisplatin in human colon and ovarian carcinoma cells

Replication and homologous recombination repair regulate DNA double-strand break formation by the antitumor alkylator ecteinascidin 743

“…HeLa cervical carcinoma cells and CEM lymphoblastic leukemia cells have been described previously (6). Recombination-deficient cells lines and their corresponding repair-proficient parental cells were generously provided by Malgorzata Zdzienicka (Leiden University Medical Center, Leiden, The Netherlands).…”

“…The cytotoxic activity of ET-743 was measured by using the MTT colorimetric assay as previously described (6). All values are averages of at least three independent experiments, each done in duplicate.…”

“…This group includes ecteinascidin-743 (ET-743, Yondelis, trabectedin), irofulven, hedamycin, and the acronycine derivative S23906. Mechanistic studies have revealed several differences in the way these compounds react with DNA-metabolizing enzymes as well as with the repair machinery (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11), which could, at least in part, explain their different activity spectra. A better understanding of the factors controlling the induction and removal of DNA damage induced by these compounds should not only facilitate their clinical application, but may also contribute to our general understanding of the structural and biological features governing adduct processing in mammalian cells.…”

“…ET-743 is a tetrahydroisoquinoline alkaloid isolated from the Caribbean sea squirt Ecteinascidia turbinata (12), pointing to marine products as a potential new source of molecules with original chemical structures and activities. ET-743 shows a broad activity spectrum toward tumor cell lines at pM and low nM concentrations (6,13) and has clinical activity toward ovarian cancer as well as soft tissue and bone sarcomas in heavily pretreated patients (14)(15)(16). In particular, ET-743 treatment is associated with a striking, long-term response in a subset of patients with otherwise chemoresistant soft tissue sarcomas (reviewed in ref.…”

Unusual illudin-type sesquiterpenoids from cultures of Agrocybe salicacola

“…10 For instance, irofulven, a derivative of natural occuring illudin S from the fruiting bodies or culture broth of several species in basidiomycetes, 11 has been admitted to clinical trails for the treatment of cancers. [12][13][14] In order to search for more illudintype sesquiterpenoids, especially ones with high cytotoxicity, we enlarged the scale of fermentation of A. salicacola, and isolated seven new illudin-type sesquiterpenoids, named as agrocybins A-G (1-7), together with three known analogues. The new structures were determined on the basis of extensive spectroscopic analysis and the X-ray crystallographic diffraction analysis, while the known compounds were identified as (2R)-2,3-dihydro-7-hydroxy-2-(hydroxymethyl)-2,4,6-trimethyl-1H-indene-5-ethanol (8), 15 illudin T (9), 9 and agrocybone (10) 8 by comparison with data reported in the literature.…”