Phenformin as prophylaxis and therapy in breast cancer xenografts

M. V. C. L. Appleyard; K. E. Murray; P. J. Coates; S. Wullschleger; S. E. Bray; N. M. Kernohan; S. Fleming; D. R. Alessi; A. M. Thompson

doi:10.1038/bjc.2012.56

Phenformin as prophylaxis and therapy in breast cancer xenografts

M. V. C. L. Appleyard (Lead / Corresponding author), K. E. Murray, P. J. Coates, S. Wullschleger, S. E. Bray, N. M. Kernohan, S. Fleming, D. R. Alessi, A. M. Thompson

Research output: Contribution to journal › Article › peer-review

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Abstract

BACKGROUND: Observations that diabetics treated with biguanide drugs have a reduced risk of developing cancer have prompted an enthusiasm for these agents as anti-cancer therapies. We sought to determine the efficacy of the biguanide phenformin in the chemoprophylaxis and in the treatment of oestrogen receptor (ER)-positive MCF7 and receptor triple-negative MDAMB231 xenografts in immunocompromised mice. We also compared the efficacy of phenformin and metformin in the treatment of MDAMB231.

METHODS: Immunocompromised mice were divided into groups: (1) phenformin administered for 2 weeks prior to cell injection; (2) established tumours treated with phenformin; (3) established tumours treated with metformin (only for MDAMB231 tumours); (4) untreated controls. Post-treatment tumours, liver and spleen were harvested for further analysis.

RESULTS: Phenformin significantly inhibited both the development and growth of MCF7 and MDAMB231 tumours, and for MDAMB231 at greater efficacy than metformin without murine toxicity. The number of mitotic figures was significantly fewer in xenografts treated with phenformin compared with controls. Results suggested that the mechanism of action of phenformin in vivo is consistent with AMPK activation.

CONCLUSION: Phenformin has clinical potential as an antineoplastic agent and should be considered for clinical trials both in ER-positive and triple-negative breast cancer. British Journal of Cancer (2012) 106, 1117-1122. doi:10.1038/bjc.2012.56 www.bjcancer.com Published online 23 February 2012 (C) 2012 Cancer Research UK

Original language	English
Pages (from-to)	1117-1122
Number of pages	6
Journal	British Journal of Cancer
Volume	106
Issue number	6
DOIs	https://doi.org/10.1038/bjc.2012.56
Publication status	Published - 13 Mar 2012

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abstract = "BACKGROUND: Observations that diabetics treated with biguanide drugs have a reduced risk of developing cancer have prompted an enthusiasm for these agents as anti-cancer therapies. We sought to determine the efficacy of the biguanide phenformin in the chemoprophylaxis and in the treatment of oestrogen receptor (ER)-positive MCF7 and receptor triple-negative MDAMB231 xenografts in immunocompromised mice. We also compared the efficacy of phenformin and metformin in the treatment of MDAMB231.METHODS: Immunocompromised mice were divided into groups: (1) phenformin administered for 2 weeks prior to cell injection; (2) established tumours treated with phenformin; (3) established tumours treated with metformin (only for MDAMB231 tumours); (4) untreated controls. Post-treatment tumours, liver and spleen were harvested for further analysis.RESULTS: Phenformin significantly inhibited both the development and growth of MCF7 and MDAMB231 tumours, and for MDAMB231 at greater efficacy than metformin without murine toxicity. The number of mitotic figures was significantly fewer in xenografts treated with phenformin compared with controls. Results suggested that the mechanism of action of phenformin in vivo is consistent with AMPK activation.CONCLUSION: Phenformin has clinical potential as an antineoplastic agent and should be considered for clinical trials both in ER-positive and triple-negative breast cancer. British Journal of Cancer (2012) 106, 1117-1122. doi:10.1038/bjc.2012.56 www.bjcancer.com Published online 23 February 2012 (C) 2012 Cancer Research UK",

author = "Appleyard, {M. V. C. L.} and Murray, {K. E.} and Coates, {P. J.} and S. Wullschleger and Bray, {S. E.} and Kernohan, {N. M.} and S. Fleming and Alessi, {D. R.} and Thompson, {A. M.}",

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AU - Appleyard, M. V. C. L.

AU - Murray, K. E.

AU - Coates, P. J.

AU - Wullschleger, S.

AU - Bray, S. E.

AU - Kernohan, N. M.

AU - Fleming, S.

AU - Alessi, D. R.

AU - Thompson, A. M.

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N2 - BACKGROUND: Observations that diabetics treated with biguanide drugs have a reduced risk of developing cancer have prompted an enthusiasm for these agents as anti-cancer therapies. We sought to determine the efficacy of the biguanide phenformin in the chemoprophylaxis and in the treatment of oestrogen receptor (ER)-positive MCF7 and receptor triple-negative MDAMB231 xenografts in immunocompromised mice. We also compared the efficacy of phenformin and metformin in the treatment of MDAMB231.METHODS: Immunocompromised mice were divided into groups: (1) phenformin administered for 2 weeks prior to cell injection; (2) established tumours treated with phenformin; (3) established tumours treated with metformin (only for MDAMB231 tumours); (4) untreated controls. Post-treatment tumours, liver and spleen were harvested for further analysis.RESULTS: Phenformin significantly inhibited both the development and growth of MCF7 and MDAMB231 tumours, and for MDAMB231 at greater efficacy than metformin without murine toxicity. The number of mitotic figures was significantly fewer in xenografts treated with phenformin compared with controls. Results suggested that the mechanism of action of phenformin in vivo is consistent with AMPK activation.CONCLUSION: Phenformin has clinical potential as an antineoplastic agent and should be considered for clinical trials both in ER-positive and triple-negative breast cancer. British Journal of Cancer (2012) 106, 1117-1122. doi:10.1038/bjc.2012.56 www.bjcancer.com Published online 23 February 2012 (C) 2012 Cancer Research UK

AB - BACKGROUND: Observations that diabetics treated with biguanide drugs have a reduced risk of developing cancer have prompted an enthusiasm for these agents as anti-cancer therapies. We sought to determine the efficacy of the biguanide phenformin in the chemoprophylaxis and in the treatment of oestrogen receptor (ER)-positive MCF7 and receptor triple-negative MDAMB231 xenografts in immunocompromised mice. We also compared the efficacy of phenformin and metformin in the treatment of MDAMB231.METHODS: Immunocompromised mice were divided into groups: (1) phenformin administered for 2 weeks prior to cell injection; (2) established tumours treated with phenformin; (3) established tumours treated with metformin (only for MDAMB231 tumours); (4) untreated controls. Post-treatment tumours, liver and spleen were harvested for further analysis.RESULTS: Phenformin significantly inhibited both the development and growth of MCF7 and MDAMB231 tumours, and for MDAMB231 at greater efficacy than metformin without murine toxicity. The number of mitotic figures was significantly fewer in xenografts treated with phenformin compared with controls. Results suggested that the mechanism of action of phenformin in vivo is consistent with AMPK activation.CONCLUSION: Phenformin has clinical potential as an antineoplastic agent and should be considered for clinical trials both in ER-positive and triple-negative breast cancer. British Journal of Cancer (2012) 106, 1117-1122. doi:10.1038/bjc.2012.56 www.bjcancer.com Published online 23 February 2012 (C) 2012 Cancer Research UK

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Phenformin as prophylaxis and therapy in breast cancer xenografts

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