2-Methoxyoestradiol-3,17-O,O-bis-sulphamate and 2-deoxy-D-glucose in combination

a potential treatment for breast and prostate cancer

S. L. C. Tagg, P. A. Foster, M. P. Leese, B. V. L. Potter, M. J. Reed, A. Purohit, S. P. Newman

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Drug combination therapy is a key strategy to improve treatment efficacy and survival of cancer patients. In this study the effects of combining 2-methoxyoestradiol-3,17-O,O-bis-sulphamate (STX140), a microtubule disruptor, with 2-deoxy-D-glucose (2DG) were assessed in MCF-7 (breast) and LNCaP (prostate) xenograft models in vivo. In mice bearing MCF-7 xenografts, daily p.o. administration of STX140 (5 mg kg(-1)) resulted in a 46% (P < 0.05) reduction of tumour volume. However, the combination of STX140 (5 mg kg(-1) p.o.) and 2DG (2 g kg(-1) i.p.) reduced tumour volume by 76% (P < 0.001). 2-Methoxyoestradiol-3,17-O,O-bis-sulphamate also reduced tumour vessel density. 2-Deoxy-D-glucose alone had no significant effect on tumour volume or vessel density. A similar benefit of the combination treatment was observed in the LNCaP prostate xenograft model. In vitro the degree of inhibition of cell proliferation by STX140 was unaffected by oxygen concentrations. In contrast, the inhibition of proliferation by 2DG was enhanced under hypoxia by 20 and 25% in MCF-7 and LNCaP cells, respectively. The combination of STX140 and 2DG in LNCaP cells under normoxia or hypoxia inhibited proliferation to a greater extent than either compound alone. These results suggest that the antiangiogenic and microtubule disruption activities of STX140 may make tumours more susceptible to inhibition of glycolysis by 2DG. This is the first study to show the benefit of combining a microtubule disruptor with 2DG in the two most common solid tumours.
Original languageEnglish
Pages (from-to)1842-1848
JournalBritish Journal of Cancer
Volume99
Issue number11
DOIs
Publication statusPublished - 2008

Fingerprint

Deoxyglucose
Prostatic Neoplasms
Breast Neoplasms
Tumor Burden
Heterografts
Microtubules
Therapeutics
Prostate
Neoplasms
sulfamic acid
2-methoxyestradiol
2-methoxyestradiol-3,17-O,O-bis(sulfamate)
MCF-7 Cells
Glycolysis
Combination Drug Therapy
Breast
Cell Proliferation
Oxygen
Survival

Keywords

  • breast
  • prostate
  • microtubule
  • 2-deoxy-D-glucose
  • O-bis-sulphamate
  • 17-O
  • 2-methoxyoestradiol-3

Cite this

2-Methoxyoestradiol-3,17-O,O-bis-sulphamate and 2-deoxy-D-glucose in combination : a potential treatment for breast and prostate cancer. / Tagg, S. L. C.; Foster, P. A.; Leese, M. P.; Potter, B. V. L.; Reed, M. J.; Purohit, A.; Newman, S. P.

In: British Journal of Cancer, Vol. 99, No. 11, 2008, p. 1842-1848.

Research output: Contribution to journalArticle

Tagg, S. L. C. ; Foster, P. A. ; Leese, M. P. ; Potter, B. V. L. ; Reed, M. J. ; Purohit, A. ; Newman, S. P. / 2-Methoxyoestradiol-3,17-O,O-bis-sulphamate and 2-deoxy-D-glucose in combination : a potential treatment for breast and prostate cancer. In: British Journal of Cancer. 2008 ; Vol. 99, No. 11. pp. 1842-1848.
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abstract = "Drug combination therapy is a key strategy to improve treatment efficacy and survival of cancer patients. In this study the effects of combining 2-methoxyoestradiol-3,17-O,O-bis-sulphamate (STX140), a microtubule disruptor, with 2-deoxy-D-glucose (2DG) were assessed in MCF-7 (breast) and LNCaP (prostate) xenograft models in vivo. In mice bearing MCF-7 xenografts, daily p.o. administration of STX140 (5 mg kg(-1)) resulted in a 46{\%} (P < 0.05) reduction of tumour volume. However, the combination of STX140 (5 mg kg(-1) p.o.) and 2DG (2 g kg(-1) i.p.) reduced tumour volume by 76{\%} (P < 0.001). 2-Methoxyoestradiol-3,17-O,O-bis-sulphamate also reduced tumour vessel density. 2-Deoxy-D-glucose alone had no significant effect on tumour volume or vessel density. A similar benefit of the combination treatment was observed in the LNCaP prostate xenograft model. In vitro the degree of inhibition of cell proliferation by STX140 was unaffected by oxygen concentrations. In contrast, the inhibition of proliferation by 2DG was enhanced under hypoxia by 20 and 25{\%} in MCF-7 and LNCaP cells, respectively. The combination of STX140 and 2DG in LNCaP cells under normoxia or hypoxia inhibited proliferation to a greater extent than either compound alone. These results suggest that the antiangiogenic and microtubule disruption activities of STX140 may make tumours more susceptible to inhibition of glycolysis by 2DG. This is the first study to show the benefit of combining a microtubule disruptor with 2DG in the two most common solid tumours.",
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AU - Foster, P. A.

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