A comparison of two orally bioavailable anti-cancer agents, IRC-110160 and STX140

Paul A. Foster, C. Stengel, Tauhid Ali, Mathew P. Leese, Barry V. L. Potter, Michael J. Reed, Atul Purohit, Simon P. Newman

Research output: Contribution to journalArticle

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Abstract

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-7(DOX)) 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.
Original languageEnglish
Pages (from-to)1483-1491
JournalAnticancer Research
Volume28
Issue number3A
Publication statusPublished - 2008

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Neoplasms
Carbonic Anhydrase II
P-Glycoprotein
Hormones
2-methoxyoestra-1,3,5(10),16-tetraene-3-carboxamide
2-methoxyestradiol-3,17-O,O-bis(sulfamate)
MCF-7 Cells
Heterografts
Nude Mice
Pharmaceutical Preparations
Antineoplastic Agents
Leukocytes
Erythrocytes
Cell Proliferation
Apoptosis
Cell Line
Growth
Population

Keywords

  • in-vivo
  • myelotoxicity
  • breast cancer
  • STX140
  • sulphamoylated derivatives
  • 2-methoxyestradiol
  • breast-cancer cells
  • inhibition
  • endogenous estrogen metabolite
  • angiogenesis
  • ENMD-1198

Cite this

Foster, P. A., Stengel, C., Ali, T., Leese, M. P., Potter, B. V. L., Reed, M. J., ... Newman, S. P. (2008). A comparison of two orally bioavailable anti-cancer agents, IRC-110160 and STX140. Anticancer Research, 28(3A), 1483-1491.

A comparison of two orally bioavailable anti-cancer agents, IRC-110160 and STX140. / Foster, Paul A.; Stengel, C.; Ali, Tauhid; Leese, Mathew P.; Potter, Barry V. L.; Reed, Michael J.; Purohit, Atul; Newman, Simon P.

In: Anticancer Research, Vol. 28, No. 3A, 2008, p. 1483-1491.

Research output: Contribution to journalArticle

Foster, PA, Stengel, C, Ali, T, Leese, MP, Potter, BVL, Reed, MJ, Purohit, A & Newman, SP 2008, 'A comparison of two orally bioavailable anti-cancer agents, IRC-110160 and STX140', Anticancer Research, vol. 28, no. 3A, pp. 1483-1491.
Foster PA, Stengel C, Ali T, Leese MP, Potter BVL, Reed MJ et al. A comparison of two orally bioavailable anti-cancer agents, IRC-110160 and STX140. Anticancer Research. 2008;28(3A):1483-1491.
Foster, Paul A. ; Stengel, C. ; Ali, Tauhid ; Leese, Mathew P. ; Potter, Barry V. L. ; Reed, Michael J. ; Purohit, Atul ; Newman, Simon P. / A comparison of two orally bioavailable anti-cancer agents, IRC-110160 and STX140. In: Anticancer Research. 2008 ; Vol. 28, No. 3A. pp. 1483-1491.
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