Metformin-induced anticancer activities: recent insights

Metformin-induced anticancer activities: recent insights AbstractMetformin is a widely used antidiabetic drug, and there is evidence among diabetic patients that metformin is a chemopreventive agent against multiple cancers. There is also evidence in human studies that metformin is a cancer chemotherapeutic agent, and several clinical trials that use metformin alone or in combination with other drugs are ongoing. In vivo and in vitro cancer cell culture studies demonstrate that metformin induces both AMPK-dependent and AMPK-independent genes/pathways that result in inhibition of cancer cell growth and migration and induction of apoptosis. The effects of metformin in cancer cells resemble the patterns observed after treatment with drugs that downregulate specificity protein 1 (Sp1), Sp3 and Sp4 or by knockdown of Sp1, Sp3 and Sp4 by RNA interference. Studies in pancreatic cancer cells clearly demonstrate that metformin decreases expression of Sp1, Sp3, Sp4 and pro-oncogenic Sp-regulated genes, demonstrating that one of the underlying mechanisms of action of metformin as an anticancer agent involves targeting of Sp transcription factors. These observations are consistent with metformin-mediated effects on genes/pathways in many other tumor types. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Biological Chemistry de Gruyter

Metformin-induced anticancer activities: recent insights

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Publisher
De Gruyter
Copyright
©2018 Walter de Gruyter GmbH, Berlin/Boston
ISSN
1437-4315
eISSN
1437-4315
D.O.I.
10.1515/hsz-2017-0271
Publisher site
See Article on Publisher Site

Abstract

AbstractMetformin is a widely used antidiabetic drug, and there is evidence among diabetic patients that metformin is a chemopreventive agent against multiple cancers. There is also evidence in human studies that metformin is a cancer chemotherapeutic agent, and several clinical trials that use metformin alone or in combination with other drugs are ongoing. In vivo and in vitro cancer cell culture studies demonstrate that metformin induces both AMPK-dependent and AMPK-independent genes/pathways that result in inhibition of cancer cell growth and migration and induction of apoptosis. The effects of metformin in cancer cells resemble the patterns observed after treatment with drugs that downregulate specificity protein 1 (Sp1), Sp3 and Sp4 or by knockdown of Sp1, Sp3 and Sp4 by RNA interference. Studies in pancreatic cancer cells clearly demonstrate that metformin decreases expression of Sp1, Sp3, Sp4 and pro-oncogenic Sp-regulated genes, demonstrating that one of the underlying mechanisms of action of metformin as an anticancer agent involves targeting of Sp transcription factors. These observations are consistent with metformin-mediated effects on genes/pathways in many other tumor types.

Journal

Biological Chemistryde Gruyter

Published: Mar 28, 2018

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