Metformin: Insights into its anticancer potential with special reference to AMPK dependent and independent pathways

Ikhlas, Shoeb; Ahmad, Masood

doi:10.1016/j.lfs.2017.07.029

Cited by 56 publications

(41 citation statements)

References 136 publications

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“…By restraining Complex I in the mitochondrial respiratory chain, MET generates cellular energy stress and thus activates AMPK . Accumulating evidence supports an anticancer effect of this drug …”

Section: Introductionmentioning

confidence: 99%

“…13 Accumulating evidence supports an anticancer effect of this drug. 14 To determine whether the AMPK pathway affects PRLoma development, we measured AMPK phosphorylation in human primary PRLoma samples, and investigated the effect and downstream effectors of AMPK agonist MET in PRLoma using BC-sensitive MMQ cells and BC-resistance GH3 cells and their xenografts as models. Our working hypotheses are that the AMPK pathway is a potential therapeutic target for PRLoma, and MET combined with BC is a potential treatment for PRLoma.…”

Section: Introductionmentioning

confidence: 99%

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Metformin inhibits growth and prolactin secretion of pituitary prolactinoma cells and xenografts

Gao

Liu

Han

et al. 2018

J Cellular Molecular Medi

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Metformin (MET) is a diabetes drug that activates AMP‐activated protein kinase (AMPK), and is suggested to have anticancer efficacy. Here, we investigated the role of AMPK signalling in prolactinoma (PRLoma), with particular respect to MET and bromocriptine (BC) as a PRLoma treatment. We analysed AMPK phosphorylation, dopamine D2 receptor (D2R), and oestrogen receptor (ER) expression in both BC‐sensitive and ‐resistant PRLoma samples; effects of the AMPK agonist MET (alone or with BC) on in vitro proliferation and apoptosis, xenograft growth and prolactin (PRL) secretion of BC‐sensitive and ‐resistant cells, and ER expression in xenografts. Some BC‐resistant PRLomas showed high D2R expression but extremely low AMPK activation. MET significantly inhibited proliferation of cultured PRLoma cells; MET + BC notably restrained their PRL secretion. MET + BC further decreased tumour growth and serum PRL levels in xenografts than BC treatment alone. ER was down‐regulated after AMPK activation in both cultured cells and xenografts. Together, we propose that the AMPK signalling pathway down‐regulates ERα and ERβ, and suppresses PRLoma growth as well as PRL secretion. Combined MET + BC is a potential treatment for PRLomas.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Metformin inhibits growth and prolactin secretion of pituitary prolactinoma cells and xenografts

Gao

Liu

Han

et al. 2018

J Cellular Molecular Medi

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“…The primary molecular targets of metformin include Complex I of the mitochondrial electron transport chain (ETC) and the adenosine monophosphate (AMP)-activated protein kinase (AMPK) (Li et al, 2018a;Mallik & Chowdhury, 2018;Vancura et al, 2018). AMPK is a heterotrimeric serine/threonine protein kinase that plays a central role in metabolism and energy regulation by restricting anabolic processes while promoting catabolic processes (Ikhlas & Ahmad, 2017;Vancura et al, 2018).…”

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confidence: 99%

Impact of metformin use on the outcomes of newly diagnosed diffuse large B‐cell lymphoma and follicular lymphoma

et al. 2019

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Summary The diabetes mellitus (DM) drug metformin targets mechanistic/mammalian target of rapamycin and inhibits lymphoma growth in vitro. We investigated whether metformin affected outcomes of newly diagnosed diffuse large B‐cell (DLBCL, n = 869) and follicular lymphoma (FL, n = 895) patients enrolled in the Mayo component of the Molecular Epidemiology Resource cohort study between 2002 and 2015. Hazard ratios (HR) and 95% confidence intervals (CIs) adjusted for age, sex, body mass index, prognostic index and treatment were used to estimate the association of metformin exposure (No DM/No metformin; DM/No metformin; DM/Metformin) with event‐free (EFS), lymphoma‐specific (LSS) and overall (OS) survival. Compared to No DM/No metformin DLBCL patients, there was no association of DM/Metformin (n = 48; HR = 1·05, 95% CI 0·59–1·89) or DM/No metformin(n = 54; HR = 1·41, 95% CI 0·88–2·26) with EFS; results were similar for LSS and OS. Compared to No DM/No metformin FL patients, there was no association of DM/Metformin (n = 37; HR = 1·16, 95% CI 0·71–1·89) or DM/No metformin (n = 19; HR = 1·16, 95% CI 0·66–2·04) with EFS; results were similar for LSS. However, DM/Metformin was associated with inferior OS (HR = 2·17; 95% CI 1·19–3·95) compared to No DM/No metformin. In conclusion, we found no evidence that metformin use was associated with improved outcomes in newly diagnosed DLBCL and FL.

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“…It has been established that Met inhibits proliferation of various neoplastic cell lines in vitro, including breast, prostatic, colon, gastric, and cervical cancers [7,8]. Currently, there is an intense ongoing research focused on molecular mechanisms behind these effects, since the implications of Met action in tumor cell are not completely understood [9].…”

Section: Introductionmentioning

confidence: 99%

Metformin in Cervical Cancer: Metabolic Reprogramming

Tyszka-Czochara¹,

Majka²

2019

Metformin [Working Title]

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The reprogrammed metabolism plays a crucial role in intensively proliferating tumor cells to meet high energetic demands and adapt to metastasis and invasion. Metformin may counteract flexible metabolic phenotype of cervical cancer cells by restraining aerobic glycolysis (Warburg effect) and promoting mitochondrial-based metabolism. Metformin inhibits master oncogene c-Myc as well as hypoxia-inducible factor 1 (HIF-1α) and suppresses its downstream glycolytic regulatory enzymes and glucose transporters. Metformin targets bioenergetics of cervical cancer cells with aggressive phenotype and regulates the expression of enzymes controlling tricarboxylic acid cycle (TCA cycle) supplementation with substrates, glucose, and glutamine. The exposition of cervical tumor cells to Metformin alleviates their migratory capacity, restrains epithelial-to-mesenchymal transition (EMT) program implementation, and elucidates oxidative stress, which results in massive cell death due to apoptosis. The metabolic alterations caused by Metformin are specific to cancer cells. In summary, Metformin exerts antitumor effect in cervical cancer cells by regulating specific molecular targets in reprogrammed metabolism. Metformin selectively modulates metabolic pathways and thus may be potentially used in new precisely targeted therapeutic strategies for cervical cancer.

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Metformin: Insights into its anticancer potential with special reference to AMPK dependent and independent pathways

Cited by 56 publications

References 136 publications

Metformin inhibits growth and prolactin secretion of pituitary prolactinoma cells and xenografts

Metformin inhibits growth and prolactin secretion of pituitary prolactinoma cells and xenografts

Impact of metformin use on the outcomes of newly diagnosed diffuse large B‐cell lymphoma and follicular lymphoma

Metformin in Cervical Cancer: Metabolic Reprogramming

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