Characterizations of irofulven cytotoxicity in combination with cisplatin and oxaliplatin in human colon, breast, and ovarian cancer cells

Abstract

Irofulven displays synergistic antiproliferative and pro-apoptotic effects when combined with oxaliplatin over a broad range of concentrations in human colon and breast cancer cells. Acquired resistance to irofulven has limited impact on the effects of cisplatin-irofulven and oxaliplatin-irofulven combinations. Based on these data, irofulven-oxaliplatin and cisplatin-irofulven combinations will be further explored in clinical trials, favoring the use schedules of oxaliplatin given prior to irofulven in patients with cancer.

Irofulven induces replication-dependent CHK2 activation related to p53 status

“…Previous studies conducted in tumor cell lines with wild-type or mutant p53 suggested that the cytotoxicity induced by irofulven is independent of p53 status [55][56][57]. In this study, the chemosensitivity to irofulven was compared in isogenic HCT116 p53+/+ and p53−/− cells.…”

Unusual illudin-type sesquiterpenoids from cultures of Agrocybe salicacola

“…The IR spectrum showed absorption at 3439 cm −1 due to the hydroxy groups. 13 C NMR data analysis suggested that 2 was also an illudin-type sesquiterpenoid as deduced from the characteristic signals at δ C 26.6 (s, C-3), 14.9 (t, C-11), and 10.0 (t, C-12) for the three-membered carbon ring and the quaternary resonance at δ C 38.2 (s, C-7). 2D NMR data analysis indicated that compound 2 was structurally resembled illudane, 16 except for the terminal double bond between C-2 and C-10 becoming saturated in 2, as supported by the HMBC correlation of δ H 0.97 (3H, d, J = 6.8 Hz, H-10) with δ C 46.8 (d, C-2), 75.8 (d, C-1), and 26.6 (s, C-3).…”

“…In the 13 C NMR data, three characteristic signals at δ C 27.6 (s, C-3), 5.3 (t, C-11), and 6.4 (t, C-12) revealed the existence of a three-membered carbon skeleton (ring A). 8,9 These information, along with the characteristic quaternary carbon resonance at δ C 37.8 (s, C-7) and four methyl groups (including two oxidated ones) led to the hypothesis that compound 1 might be an illudin-type sesquiterpenoid possessing a 3/6/5 carbon skeleton (rings A-C as shown in Figure 1) as those reported previously from the same resource.…”

“…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.…”

Tetraarsenic oxide and cisplatin induce apoptotic synergism in cervical cancer

“…Various combination regimens have become a major strategy for overcoming drug resistance and improving response and cure rates (34)(35)(36), and these should be able to decrease the adverse effects of the drugs. Therefore, drug interactions may be fully recognized when TAO + cisplatin combination chemotherapy is administered to patients with advanced cervical cancer.…”