Article
Pharmacology & Pharmacy
Qiongfeng Chen, Yaqun Wang, Linna Sheng, Yonghong Huang
Summary: This study found that adenosine monophosphate-activated protein kinase (AMPK) and its activator metformin play a significant role in the regulation of fibroblast activation and pulmonary fibrosis through inhibiting the bone morphogenetic protein (BMP) pathway.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Endocrinology & Metabolism
Calum Forteath, Ify Mordi, Raid Nisr, Erika J. Gutierrez-Lara, Noor Alqurashi, Iain R. Phair, Amy R. Cameron, Craig Beall, Ibrahim Bahr, Mohapradeep Mohan, Aaron K. F. Wong, Adel Dihoum, Anwar Mohammad, Colin N. A. Palmer, Douglas Lamont, Kei Sakamoto, Benoit Viollet, Marc Foretz, Chim C. Lang, Graham Rena
Summary: Using cellular approaches and proteomics, we found that metformin therapy for diabetes alters the regulation of branched chain amino acids through the suppression of the amino acid transporter SNAT2.
MOLECULAR METABOLISM
(2023)
Article
Pharmacology & Pharmacy
Xuan Gu, Yong-Yue Han, Chong-Yang Yang, Hui-Min Ji, Yue-Jiao Lan, Yu-Qian Bi, Cheng Zheng, Jiao Qu, Ming-Han Cheng, Jian Gao
Summary: In this study, the relationship between AMPK and FOXM1 in fibroblast proliferation-mediated pulmonary fibrosis (PF) was investigated. The results showed that activation of AMPK by metformin down-regulated FOXM1 and alleviated PF in mouse models, while inhibition of AMPK enhanced fibroblast proliferation. This study provides new insights into potential treatment approaches for PF involving the regulation of FOXM1 by AMPK.
PHARMACOLOGICAL RESEARCH
(2021)
Review
Biochemistry & Molecular Biology
Mehdi Sanati, Samaneh Aminyavari, Hamid Mollazadeh, Ali Motamed-Sanaye, Bahram Bibak, Elmira Mohtashami, Yong Teng, Amir R. R. Afshari, Amirhossein Sahebkar
Summary: This research reviewed the literature to assess the connection between metformin's anticancer properties and the development of glioblastoma multiforme (GBM). The comprehensive review found that metformin not only inhibits tumor growth by activating the AMPK pathway, but also induces cell apoptosis, inhibits cell proliferation and metastasis, and enhances chemo-radio-sensitizing behavior against GBM through other mechanisms. Further research is needed to explore the potential of metformin-based therapeutics for GBM and the challenges they may face.
CURRENT MEDICINAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Lorea Zubiaga, Olivier Briand, Florent Auger, Veronique Touche, Thomas Hubert, Julien Thevenet, Camille Marciniak, Audrey Quenon, Caroline Bonner, Simon Peschard, Violeta Raverdy, Mehdi Daoudi, Julie Kerr-Conte, Gianni Pasquetti, Hermann Koepsell, Daniela Zdzieblo, Markus Muhlemann, Bernard Thorens, Nathalie D. Delzenne, Laure B. Bindels, Benoit Deprez, Marie C. Vantyghem, Blandine Laferrere, Bart Staels, Damien Huglo, Sophie Lestavel, Francois Pattou
Summary: Metformin (MET) is a commonly prescribed antidiabetic drug, and recent data suggests that its main mechanism of action is through the gut. It reduces the expression of sodium-glucose transporter 1 (SGLT1) in enterocytes, leading to decreased glucose absorption and transiently lowering post-prandial glucose response.
Review
Chemistry, Medicinal
Vincenzo Sorrenti, Francesca Benedetti, Alessandro Buriani, Stefano Fortinguerra, Giada Caudullo, Sergio Davinelli, Davide Zella, Giovanni Scapagnini
Summary: Aging is a result of the dysregulation of multiple molecular pathways, with mTOR and AMPK signaling playing a role in cellular senescence. Poor nutritional balance is a driving factor in immunosenescence progression, and nutraceutical and pharmacological interventions can help maintain optimal biological response. Compounds like resveratrol, rapamycin, and metformin have shown positive effects in healthy aging.
Article
Cell Biology
Meichen Ma, Yue Pan, Yue Zhang, Mei Yang, Ying Xi, Baoxu Lin, Wudi Hao, Jianhua Liu, Lina Wu, Yong Liu, Xiaosong Qin
Summary: The research findings suggest that the combination of metformin and rapamycin can reduce proteinuria and improve renal fibrosis in the context of idiopathic membranous nephropathy (IMN) by regulating the AMPK/mTOR autophagy signaling pathway.
JOURNAL OF CELL COMMUNICATION AND SIGNALING
(2023)
Review
Medicine, Research & Experimental
Guangli Lu, Zhen Wu, Jia Shang, Zhenxing Xie, Chaoran Chen, Chuning Zhang
Summary: Metformin is the first-line option for treating diabetic patients and has various pharmacological actions, including antitumor, anti-aging, and ovarian protection effects. Recent research has shown that autophagy is a crucial mechanism through which metformin exerts its pharmacological actions, although the effects on autophagy remain inconsistent.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Review
Cell Biology
Edward J. Calabrese, Evgenios Agathokleous, Rachna Kapoor, Gaurav Dhawan, Walter J. Kozumbo, Vittorio Calabrese
Summary: Metformin induced hormetic biphasic dose responses across multiple organ systems and cell types, enhancing resilience to chemical stresses through an anti-inflammatory molecular network, thereby delaying the onset and progression of neurodegenerative and chronic diseases.
AGEING RESEARCH REVIEWS
(2021)
Article
Cell Biology
Mengmeng Chen, Yushan Fu, Xu Wang, Ruitong Wu, Dongmei Su, Nan Zhou, Yanhua Qi
Summary: The senescence of lens epithelial cells (LECs) is a major factor leading to age-related cataract (ARC). This study aimed to investigate the mechanism of ARC formation and explore the anti-aging effect of metformin (MET) on ARC. The results showed that MET effectively alleviated the senescence of LECs and the formation of ARC probably through inactivation of the AMPK pathway and augmentation of autophagy.
CELL DEATH DISCOVERY
(2022)
Review
Biochemistry & Molecular Biology
Joa Kim, Yun-Sung Kim, Sung-Hwan Park
Summary: Metformin, a first-line agent for type 2 diabetes, shows potential as a treatment strategy for Sjogren's syndrome by modulating AMPK and mTOR pathways to enhance immunoregulatory response and ameliorate salivary gland function.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Dianpeng Zheng, Yaowen Mao, Yinglong Gao, Feng He, Jun Ma
Summary: The cellular response to nutrient deprivation is not well known, but it has been observed that glucose withdrawal does not immediately halt the cell cycle like the removal of amino acids or glutamine does. Daughter cells from mother cells experiencing glucose withdrawal in S phase have the choice of proliferation or quiescence, while those experiencing it in G1 phase predominantly enter quiescence. This difference is due to the accumulation of p21 protein during G2/M in the latter cells, which can be degraded to allow daughter cells to enter S phase but with increased DNA damage.
Article
Cell Biology
Hong-Yue Lai, Hsin-Hwa Tsai, Chia-Jui Yen, Liang-Yi Hung, Ching-Chieh Yang, Chung-Han Ho, Hsin-Yin Liang, Feng-Wei Chen, Chien-Feng Li, Ju-Ming Wang
Summary: This study found that HCC patients receiving sorafenib with HBV were at higher risk of mortality, and high EGFR expression was linked to HBV-induced sorafenib resistance. Additionally, AMPK/CEBPD-activated autophagy could be a potent strategy for improving the efficacy of sorafenib in HCC patients.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Cell Biology
Hong-Yue Lai, Hsin-Hwa Tsai, Chia-Jui Yen, Liang-Yi Hung, Ching-Chieh Yang, Chung-Han Ho, Hsin-Yin Liang, Feng-Wei Chen, Chien-Feng Li, Ju-Ming Wang
Summary: Activation of autophagy can both promote survival of residual cancer cells and lead to cell death, with implications for sorafenib resistance in hepatocellular carcinoma patients. High EGFR expression is linked to HBV-induced sorafenib resistance, with AMPK/CEBPD-activated autophagy presenting a potential strategy for enhancing sorafenib efficacy.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Pharmacology & Pharmacy
Wang Liao, Jiaxin Xu, Bo Li, Yuting Ruan, Tian Li, Jun Liu
Summary: Alzheimer's disease is a prevalent neurodegenerative disease with no effective treatment. Metformin, a medication for Type 2 Diabetes Mellitus, has shown beneficial effects on cognitive function, but current evidence remains ambiguous and conflicting.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Oncology
Jihye Kim, Chen Yuan, Ana Babic, Ying Bao, Clary B. Clish, Michael N. Pollak, Laufey T. Amundadottir, Alison P. Klein, Rachael Z. Stolzenberg-Solomon, Pari V. Pandharipande, Lauren K. Brais, Marisa W. Welch, Kimmie Ng, Edward L. Giovannucci, Howard D. Sesso, Joann E. Manson, Meir J. Stampfer, Charles S. Fuchs, Brian M. Wolpin, Peter Kraft
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
(2020)
Article
Oncology
Michael N. Pollak, William D. Foulkes, Jessica G. Mancuso
CANCER PREVENTION RESEARCH
(2020)
Article
Oncology
Neil M. Iyengar, Xi Kathy Zhou, Hillary Mendieta, Dilip D. Giri, Omar El-Hely, Lisle Winston, Domenick J. Falcone, Hanhan Wang, Lingsong Meng, Jonathan Landa, Michael Pollak, Laurie Kirstein, Monica Morrow, Andrew J. Dannenberg
Summary: Excess body fat and sedentary behavior are associated with increased breast cancer risk and mortality. The study found that adiposity and lack of exercise impact the breast microenvironment and circulating metabo-inflammatory factors, suggesting the importance of lifestyle interventions targeting adiposity to prevent tumor growth.
CANCER PREVENTION RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Sirui Zhou, Guillaume Butler-Laporte, Tomoko Nakanishi, David R. Morrison, Jonathan Afilalo, Marc Afilalo, Laetitia Laurent, Maik Pietzner, Nicola Kerrison, Kaiqiong Zhao, Elsa Brunet-Ratnasingham, Danielle Henry, Nofar Kimchi, Zaman Afrasiabi, Nardin Rezk, Meriem Bouab, Louis Petitjean, Charlotte Guzman, Xiaoqing Xue, Chris Tselios, Branka Vulesevic, Olumide Adeleye, Tala Abdullah, Noor Almamlouk, Yiheng Chen, Michael Chasse, Madeleine Durand, Clare Paterson, Johan Normark, Robert Frithiof, Miklos Lipcsey, Michael Hultstrom, Celia M. T. Greenwood, Hugo Zeberg, Claudia Langenberg, Elin Thysell, Michael Pollak, Vincent Mooser, Vincenzo Forgetta, Daniel E. Kaufmann, J. Brent Richards
Summary: The study identified that increased levels of OAS1 protein are associated with reduced susceptibility and severity of COVID-19, providing evidence for a protective role of OAS1 in adverse outcomes. This suggests that pharmacological agents that increase OAS1 levels could be prioritized for drug development against COVID-19. The variant of the OAS1 gene associated with decreased risk of death in COVID-19 patients encodes an enzyme critical for the innate immune response to viral infections.
Article
Oncology
Ann H. Rosendahl, Sofie Bjorner, Maria Ygland Rodstrom, Karin Jirstrom, Signe Borgquist, Christian Ingvar, Michael N. Pollak, Helena Jernstrom
Summary: The study found that circulating levels of IGF-I and IGFBP-3 in breast cancer patients are significantly associated with recurrence-risk, while the correlation with IGFBP-7 levels is weaker. There is a significant interaction between IGFBP-7 levels and recurrence-risk in patients with IGF-IRm positivity.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Neil M. Iyengar, Xi Kathy Zhou, Hillary Mendieta, Omar El-Hely, Dilip D. Giri, Lisle Winston, Domenick J. Falcone, Hanhan Wang, Lingsong Meng, Taehoon Ha, Michael Pollak, Monica Morrow, Andrew J. Dannenberg
Summary: Obesity is associated with increased levels of aromatase and inflammation in the breasts of pre-menopausal BRCA1/2 mutation carriers, potentially contributing to the higher risk of early-onset breast cancer in this population. This highlights the importance of understanding the molecular mechanisms underlying the relationship between obesity and breast cancer risk in BRCA1/2 mutation carriers.
Article
Oncology
David Papadopoli, Oro Uchenunu, Ranveer Palia, Nabila Chekkal, Laura Hulea, Ivan Topisirovic, Michael Pollak, Julie St-Pierre
Summary: Studies have shown that the SGLT2 inhibitor canagliflozin can inhibit the proliferation of breast cancer cells by limiting glucose uptake, and this effect is independent of glucose availability and the level of SGLT2 expression. Canagliflozin inhibits cell proliferation by reducing oxygen consumption and glutamine metabolism, which fuel respiration. This represents a previously unexpected mechanism of its potential antineoplastic action.
Review
Biochemistry & Molecular Biology
David Papadopoli, Michael Pollak, Ivan Topisirovic
Summary: Malignant transformation and tumor progression are closely related to perturbations in metabolic programs, with GSK3 playing a crucial role in regulating metabolic processes in cancer, affecting protein and lipid synthesis, glucose and mitochondrial metabolism, as well as autophagy.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2021)
Article
Oncology
Byuri Angela Cho, Neil M. Iyengar, Xi Kathy Zhou, Monica Morrow, Dilip D. Giri, Akanksha Verma, Olivier Elemento, Michael Pollak, Andrew J. Dannenberg
Summary: Obesity and breast white adipose tissue inflammation are associated with increased risk of post-menopausal breast cancer. Through analyzing molecular changes in breast tissues and blood biomarkers, this study helps to explain the link between obesity and breast cancer, highlighting the potential utility of blood biomarkers in determining risk and prognosis.
Article
Biochemistry & Molecular Biology
Sebastian Igelmann, Frederic Lessard, Oro Uchenunu, Jacob Bouchard, Ana Fernandez-Ruiz, Marie-Camille Rowell, Stephane Lopes-Paciencia, David Papadopoli, Aurelien Fouillen, Katia Julissa Ponce, Genevieve Huot, Lian Mignacca, Mehdi Benfdil, Paloma Kalegari, Haytham M. Wahba, Jan Pencik, Nhung Vuong, Jordan Quenneville, Jordan Guillon, Veronique Bourdeau, Laura Hulea, Etienne Gagnon, Lukas Kenner, Richard Moriggl, Antonio Nanci, Michael N. Pollak, James G. Omichinski, Ivan Topisirovic, Gerardo Ferbeyre
Summary: A multi-enzymatic complex, known as hydride transfer complex (HTC), is reported to reprogram NAD metabolism and overcome cellular senescence in cancer or hypoxic cells. This complex is highly expressed in prostate cancer models and its inactivation triggers senescence, while its exogenous expression can bypass senescence and cooperate with oncogenic RAS to transform primary cells.
Article
Multidisciplinary Sciences
Stephanie P. Totten, Young Kyuen Im, Eduardo Cepeda Canedo, Ouafa Najyb, Alice Nguyen, Steven Hebert, Ryuhjin Ahn, Kyle Lewis, Benjamin Lebeau, Rachel La Selva, Valerie Sabourin, Constanza Martinez, Paul Savage, Hellen Kuasne, Daina Avizonis, Nancy Santos Martinez, Catherine Chabot, Adriana Aguilar-Mahecha, Marie-Line Goulet, Matthew Dankner, Michael Witcher, Kevin Petrecca, Mark Basik, Michael Pollak, Ivan Topisirovic, Rongtuan Lin, Peter M. Siegel, Claudia L. Kleinman, Morag Park, Julie St-Pierre, Josie Ursini-Siegel
Summary: Bioenergetic perturbations and oxidative stress play important roles in promoting neoplastic growth, requiring compensatory increase in ROS scavengers. In addition, inflammatory mediators can enhance drug cytotoxicity through STAT1-mediated downregulation of ROS scavengers.
NATURE COMMUNICATIONS
(2021)
Article
Oncology
Stephanie M. Wong, Lissa Ajjamada, Anna C. Weiss, Ipshita Prakash, Sonia Skamene, Jean Francois Boileau, Michael N. Pollak, Mark Basik
Summary: Breast cancers in women who previously received radiation therapy for HL are characterized by earlier onset disease, although most remain estrogen receptor-positive and have early stage disease at presentation.
Article
Oncology
Talia Malagon, Jean H. E. Yong, Parker Tope, Wilson H. Miller, Eduardo L. Franco
Summary: This study used a microsimulation model to estimate the long-term impacts of cancer care disruptions during the COVID-19 pandemic in Canada. It predicted over 21,000 additional cancer deaths between 2020 and 2030, with the potential to mitigate these losses by increasing diagnostic and treatment capacity in the short term.
INTERNATIONAL JOURNAL OF CANCER
(2022)
Article
Oncology
Frank A. Sinicrope, Qian Shi, Thomas C. Smyrk, Richard M. Goldberg, Steven J. Cohen, Sharlene Gill, Morton S. Kahlenberg, Suresh Nair, Anthony F. Shield, Balkrishna N. Jahagirdar, Sawyer B. Jacobson, Nathan R. Foster, Michael N. Pollak, Steven R. Alberts
Summary: The study revealed a significant association between lower circulating adiponectin levels and increased TIL densities in colon cancer patients, indicating an enhanced anti-tumor immune response. However, neither adiponectin nor 25(OH)D were independently prognostic factors for patient outcomes.
JNCI CANCER SPECTRUM
(2021)
Article
Oncology
Brendan J. Guercio, Sui Zhang, Fang-Shu Ou, Alan P. Venook, Donna Niedzwiecki, Heinz-Josef Lenz, Federico Innocenti, Michael N. Pollak, Andrew B. Nixon, Brian C. Mullen, Bert H. O'Neil, James E. Shaw, Blase N. Polite, Al Bowen Benson, James N. Atkins, Richard M. Goldberg, Justin C. Brown, Eileen M. O'Reilly, Robert J. Mayer, Charles D. Blanke, Charles S. Fuchs, Jeffrey A. Meyerhardt
Summary: In patients with metastatic colorectal cancer, high levels of plasma IGFBP-3 and low levels of IGFBP-7 were associated with longer overall survival and progression-free survival. Extreme levels of adiponectin were linked to shorter progression-free survival, suggesting potential implications for prognostic and therapeutic innovation.
JNCI CANCER SPECTRUM
(2021)