PMID- 18630502
OWN - NLM
STAT- MEDLINE
DCOM- 20080725
LR  - 20130520
IS  - 0250-7005 (Print)
IS  - 0250-7005 (Linking)
VI  - 28
IP  - 3A
DP  - 2008 May-Jun
TI  - A comparison of two orally bioavailable anti-cancer agents, IRC-110160 and 
      STX140.
PG  - 1483-91
AB  - This study characterises two recently developed anticancer agents in vitro and in 
      vivo, 2-methoxyoestra-1,3,5(10), 16-tetraene-3-carboxamide (IRC-110160) and 
      STX140. MATERIALS AND METHODS: Hormone-dependent (MCF-7), hormone-independent 
      (MDA-MB-231) and P-glycoprotein overexpressing (MCF-7Dox) cells were used for 
      proliferation experiments. For the tumour efficacy studies, female nude mice were 
      inoculated with MDA-MB-231 cells. RESULTS: IRC-110160 is a potent inhibitor of 
      both MCF-7 and MDA-MB-231 cell proliferation. Furthermore, the potency of 
      IRC-110160 was unaffected by the over-expression of the P-glycoprotein drug 
      efflux pump. IRC-110160 and 2-methoxyoestradiol-3,17-O,O-bis-sulfamate (STX140) 
      induced apoptosis in a similar timeframe in the MDA-MB-231 cell line, but only 
      STX140 caused G2/M arrest in these cells. In the MDA-MB-231 xenograft model 300 
      mg/kg p.o. (daily) of IRC-110160 and 20 mg/kg p.o. STX140 (daily) both completely 
      inhibited tumour growth; however some toxicity was observed with IRC-110160. 
      After 28 days of daily dosing STX140 (20 mg/kg p.o.) had minimal effect on the 
      white blood population of mice with tumours. The masking of STX140 from white 
      blood cells may be due to its interaction with carbonic anhydrase II (CAII) in 
      the red blood cells. In contrast to STX140, IRC-110160 does not inhibit CAII. 
      These studies highlight the activity of two orally bioavailable anti-cancer 
      agents one of which, STX140, may offer a significant clinical advantage over 
      existing drugs as a common dose limiting factor, haemotoxicity, may be minimised.
FAU - Foster, Paul A
AU  - Foster PA
AD  - Endocrinology and Metabolic Medicine and Sterix Ltd., Faculty of Medicine, 
      Imperial College London, St. Mary's Hospital, London W2 1NY, UK.
FAU - Stengel, C
AU  - Stengel C
FAU - Ali, Tauhid
AU  - Ali T
FAU - Leese, Mathew P
AU  - Leese MP
FAU - Potter, Barry V L
AU  - Potter BV
FAU - Reed, Michael J
AU  - Reed MJ
FAU - Purohit, Atul
AU  - Purohit A
FAU - Newman, Simon P
AU  - Newman SP
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Greece
TA  - Anticancer Res
JT  - Anticancer research
JID - 8102988
RN  - 0 (2-methoxyestradiol-3,17-O,O-bis(sulfamate))
RN  - 0 (2-methoxyoestra-1,3,5(10),16-tetraene-3-carboxamide)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Estrenes)
RN  - 0 (Tubulin)
SB  - IM
MH  - Administration, Oral
MH  - Animals
MH  - Antineoplastic Agents/*pharmacology
MH  - Apoptosis/drug effects
MH  - Breast Neoplasms/*drug therapy/pathology
MH  - Cell Cycle/drug effects
MH  - Cell Growth Processes/drug effects
MH  - Cell Line, Tumor
MH  - Coculture Techniques
MH  - Drug Screening Assays, Antitumor
MH  - Endothelial Cells/cytology/drug effects
MH  - Estrenes/*pharmacology/toxicity
MH  - Female
MH  - Fibroblasts/cytology
MH  - Humans
MH  - Mice
MH  - Neoplasms, Hormone-Dependent/*drug therapy/pathology
MH  - Neovascularization, Pathologic/drug therapy
MH  - Tubulin/metabolism
MH  - Xenograft Model Antitumor Assays
EDAT- 2008/07/18 09:00
MHDA- 2008/07/26 09:00
CRDT- 2008/07/18 09:00
PHST- 2008/07/18 09:00 [pubmed]
PHST- 2008/07/26 09:00 [medline]
PHST- 2008/07/18 09:00 [entrez]
PST - ppublish
SO  - Anticancer Res. 2008 May-Jun;28(3A):1483-91.