TY - JOUR
T1 - Metformin-induced anticancer activities
T2 - Recent insights
AU - Safe, Stephen
AU - Nair, Vijayalekshmi
AU - Karki, Keshav
N1 - Funding Information:
The financial assistance of the National Institutes of Health (P30-ES023512, S. Safe), Funder Id: 10.13039/100000066, Texas AgriLife Research (S. Safe) and Sid Kyle Chair endowment (S. Safe) is gratefully acknowledged.
Publisher Copyright:
© 2018 Walter de Gruyter GmbH. All rights reserved.
Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2018/3/28
Y1 - 2018/3/28
N2 - Metformin 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.
AB - Metformin 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.
KW - Chemoprevention
KW - Chemotherapeutic
KW - Metformin
KW - Sp transcription factors
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U2 - 10.1515/hsz-2017-0271
DO - 10.1515/hsz-2017-0271
M3 - Review article
C2 - 29272251
AN - SCOPUS:85040330150
VL - 399
SP - 321
EP - 335
JO - Biological Chemistry
JF - Biological Chemistry
SN - 1431-6730
IS - 4
ER -