کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2001401 | 1066036 | 2008 | 8 صفحه PDF | دانلود رایگان |
Nitric oxide synthase (NOS) has been shown to be overexpressed in a number of human tumors compared to normal tissues and therefore potentially represents an exploitable target in future anticancer therapies. To achieve this, there will be a need to profile tumors to identify those expressing high levels of NOS; alternatively, endogenous (low) levels of NOS could be modulated by induction or through gene therapy approaches. NOS consists of a reductase domain which shares a high degree of sequence homology with P450 reductase and this domain supplies reducing equivalents to a haem containing oxygenase domain that is responsible for the production of nitric oxide. Thus, there are a number of routes of exploitation. Firstly, to take advantage of the reductase domain to activate bioreductive drugs as has been exemplified with tirapazamine and now extended to AQ4N (1,4-bis{2-(dimethylamino-N-oxide)ethylamino}5,8-dihydroxy-anthracene-9,10-dione). Secondly, to take advantage of nitric oxide production for its ability to increase the sensitivity of resistant hypoxic cells to radiation. Lastly, to utilize inhibition of HIF-1 to amplify NO based therapies. In this review we provide examples/evidence of how these objectives can be achieved.
Journal: Nitric Oxide - Volume 19, Issue 2, September 2008, Pages 217–224