Activity profile of the novel aziridinylbenzoquinones MeDZQ and RH1 in human tumour xenografts.
AffiliationCancer Research UK, Edinburgh Medical Oncology Unit, Western General Hospital, Edinburgh, EH4 2XR, U.K. firstname.lastname@example.org
MetadataShow full item record
AbstractBACKGROUND: RH1 and MeDZQ represent novel aziridinylbenzoquinones that can be activated by DT-diaphorase to form unique DNA lesions. RH1 is due to enter a phase 1 clinical trial in the United Kingdom in the summer of 2003, where pharmacodynamic monitoring of DT-diaphorase will be performed. MATERIALS AND METHODS: The antitumour efficacy of RH1 and MeDZQ has been studied in 4 human xenografts (3 non-small cell lung cancer and 1 colon cancer), and compared to the level of constitutive DT-Diaphorase activity measured by the DCPIP assay. RESULTS: The 4 xenografts exhibited a wide range of DT-diaphorase activity (4.8-303 nmol/min/mg). Greater antitumour activity was recorded in the xenografts expressing high levels of DT-diaphorase (e.g. NX002, DT-diaphorase activity, 303 +/- 52 nmol/min/mg, T/C to MeDZQ, 33.3% and to RH1, 43.4%). CONCLUSION: These data add in vivo support to a role for DT-Diaphorase in the antitumour activity of RH1.
CitationActivity profile of the novel aziridinylbenzoquinones MeDZQ and RH1 in human tumour xenografts., 23 (5A):3979-83 Anticancer Res.
- A new screening system for NAD(P)H:quinone oxidoreductase (NQO1)-directed antitumor quinones: identification of a new aziridinylbenzoquinone, RH1, as a NQO1-directed antitumor agent.
- Authors: Winski SL, Hargreaves RH, Butler J, Ross D
- Issue date: 1998 Dec
- The effect of functional groups on reduction and activation of quinone bioreductive agents by DT-diaphorase.
- Authors: Fourie J, Oleschuk CJ, Guziec F Jr, Guziec L, Fiterman DJ, Monterrosa C, Begleiter A
- Issue date: 2002 Feb
- Effect of NQO1 induction on the antitumor activity of RH1 in human tumors in vitro and in vivo.
- Authors: Digby T, Leith MK, Thliveris JA, Begleiter A
- Issue date: 2005 Sep
- Elevated DT-diaphorase activity and messenger RNA content in human non-small cell lung carcinoma: relationship to the response of lung tumor xenografts to mitomycin Cł.
- Authors: Malkinson AM, Siegel D, Forrest GL, Gazdar AF, Oie HK, Chan DC, Bunn PA, Mabry M, Dykes DJ, Harrison SD
- Issue date: 1992 Sep 1
- Nicotinamide adenine dinucleotide (phosphate): quinone oxidoreductase (DT-diaphorase) as a target for bioreductive antitumor quinones: quinone cytotoxicity and selectivity in human lung and breast cancer cell lines.
- Authors: Beall HD, Murphy AM, Siegel D, Hargreaves RH, Butler J, Ross D
- Issue date: 1995 Sep