Article
Biochemistry & Molecular Biology
Malgorzata Dolowy, Josef Jampilek, Katarzyna Bober-Majnusz
Summary: The study utilized TLC technique to investigate the lipophilicity parameters of metformin and phenformin, confirming their poor lipophilicity. It emphasized the need for optimizing chromatographic conditions to obtain reliable results.
Article
Multidisciplinary Sciences
Traci E. LaMoia, Gina M. Butrico, Hasini A. Kalpage, Leigh Goedeke, Brandon T. Hubbard, Daniel F. Vatner, Rafael C. Gaspar, Xian-Man Zhang, Gary W. Cline, Keita Nakahara, Seungwan Woo, Atsuhiro Shimada, Maik Huttemann, Gerald Shulman
Summary: Metformin reduces hepatic gluconeogenesis by inhibiting complex IV to decrease the function of GPD2, leading to a decrease in glycerol-derived hepatic gluconeogenesis.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Monica Cejuela, Begona Martin-Castillo, Javier A. Menendez, Sonia Pernas
Summary: Breast cancer is the most common cancer among women worldwide, and metabolic traits associated with type 2 diabetes such as hyperglycemia, hyperinsulinemia, inflammation, oxidative stress, and obesity are known risk factors. Metformin, a widely prescribed medication for diabetes, has been suggested to have anti-tumor effects based on previous studies. However, recent randomized controlled trials have shown disappointing results, particularly in metastatic breast cancer. This article reviews the mechanisms of action of metformin, discusses past and current clinical trials, and briefly explores future perspectives for incorporating metformin into the prevention and treatment of breast cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Medicine, Research & Experimental
Morteza Gholami, Zeynab Nickhah Klashami, Pirooz Ebrahimi, Amir Ali Mahboobipour, Amir Salehi Farid, Aida Vahidi, Marziyeh Zoughi, Mojgan Asadi, Mahsa M. Amoli
Summary: This comprehensive study aims to review the association between long non-coding RNAs (lncRNAs) and breast cancer (BC) features, and identify metformin-regulated lncRNAs and their mechanisms of action in BC and other types of cancers. The study found that metformin affects BC by regulating five BC-associated lncRNAs including GAS5, HOTAIR, MALAT1, and H19, through several molecular mechanisms. Additionally, metformin also acts on other types of cancers by regulating ten lncRNAs.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Article
Neurosciences
Natasa Svirskiene, Katryna Pampuscenko, Gytis Svirskis, Vilmante Borutaite
Summary: The study found that metformin and phenformin have different effects on calcium homeostasis in hypoxia-affected neurons. Pre-treatment with metformin increased signal amplitude and decreased spontaneous signal frequency, while phenformin did not. Both drugs, however, accelerated the decay of calcium concentration in hypoxia-affected neurons.
Article
Biochemistry & Molecular Biology
Silvija Jankeviciute, Natasa Svirskiene, Gytis Svirskis, Vilmante Borutaite
Summary: The study revealed that microglial cells exhibit changes in Ca2+ signaling when mitochondrial respiration is inhibited under both normoxic and mild-hypoxic conditions, and different effects are observed with the drugs metformin and rotenone. The fast action of metformin and rotenone in normoxia contrasts with their slow action during mild-hypoxia, suggesting activation of distinct signaling pathways.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Medicine, Research & Experimental
Sara S. Bashraheel, Hadeel Kheraldine, Sarah Khalaf, Ala-Eddin Al Moustafa
Summary: Due to the strong association between diabetes and cancer incidents, several anti-diabetic drugs, including metformin, have been examined for their anticancer activity. Metformin exhibits anticancer activity by impacting different molecular pathways and indirectly inhibiting IGF-1R signaling in breast malignancy. Breast cancer, especially the HER2-positive subtype, is highly aggressive with a high rate of lymph node metastasis. This review summarizes the association between diabetes and human cancer, focusing on metformin's anticancer activity and combination therapy strategies in HER2-positive breast cancer.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Biochemical Research Methods
Rui Zhang, Ling-yi Zhao, Chen-yang Zhao, Ming Wang, Si-rui Liu, Jian-chu Li, Rui-na Zhao, Ruo-jiao Wang, Fang Yang, Lei Zhu, Xu-jin He, Chang-hui Li, Yu-xin Jiang, Meng Yang
Summary: The study utilized a handheld dual-modal PA/US imaging system to examine benign and malignant breast nodules, revealing significant differences in the distribution of PA signals between the two. Both quantitative and semi-quantitative analyses showed promising diagnostic potential for breast cancer, highlighting the clinical utility of PA parameters in diagnosis.
BIOMEDICAL OPTICS EXPRESS
(2021)
Article
Biochemistry & Molecular Biology
Miran Rada, Lucyna Krzywon, Stephanie Petrillo, Anthoula Lazaris, Peter Metrakos
Summary: This retrospective cohort study examined the role of metformin in colorectal cancer liver metastases (CRCLM). Among 108 patients, 20 patients used metformin and showed significantly lower incidence of vessel co-opting RHGP tumors, recurrence rate, and extrahepatic metastases. Metformin users also had significantly higher survival outcome. These findings suggest that metformin administration may be associated with better prognosis of CRCLM.
Article
Polymer Science
Anindita De, Ashish Wadhwani, Parikshit Sauraj, Parikshit Roychowdhury, Ji Hee Kang, Young Tag Ko, Gowthamarajan Kuppusamy
Summary: The Warburg effect offers a new approach to cancer metabolism treatment. GLUT1 overexpression, AMPK activation, and mTOR downregulation are identified as biomarkers of abnormal cancer cell metabolism. A combination therapy of WZB117 (a GLUT1 inhibitor), OCMC (O-carboxymethyl-chitosan), and MET is proposed for simultaneous targeting of GLUT1 and mTOR to alter breast cancer metabolism. The strategy overcomes the limitations of MET monotherapy by synergistically targeting mTOR and BCL2.
Article
Oncology
Jingjing Yang, Yulu Zhou, Shuduo Xie, Ji Wang, Zhaoqing Li, Lini Chen, Misha Mao, Cong Chen, Aihua Huang, Yongxia Chen, Xun Zhang, Noor Ul Hassan Khan, Linbo Wang, Jichun Zhou
Summary: This study demonstrates that metformin induces ferroptosis in an AMPK-independent manner to suppress tumor growth. Mechanistically, metformin increases the intracellular Fe2+ and lipid ROS levels by targeting the UFMylation process of SLC7A11. Additionally, combining metformin with the x(c)(-) inhibitor sulfasalazine synergistically induces ferroptosis and inhibits the proliferation of breast cancer cells.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2021)
Review
Chemistry, Medicinal
Daniil A. Rusanov, Jiaying Zou, Maria V. Babak
Summary: Metformin is a widely used drug for the treatment of type 2 diabetes, and it has diverse biological properties such as anticancer and antimicrobial activities. Recent studies have shown that the mechanism of action of metformin is linked to its binding to metals. Coordination of metformin to metal centers improves the pharmacological profile of the drug and allows for selective activation of prodrugs and reduced off-target toxicity.
Article
Medicine, Research & Experimental
Domenica Scordamaglia, Francesca Cirillo, Marianna Talia, Maria Francesca Santolla, Damiano Cosimo Rigiracciolo, Lucia Muglia, Azzurra Zicarelli, Salvatore De Rosis, Francesca Giordano, Anna Maria Miglietta, Ernestina Marianna De Francesco, Veronica Vella, Antonino Belfiore, Rosamaria Lappano, Marcello Maggiolini
Summary: This study investigated the role of metformin in inhibiting the growth and metastasis of breast cancer cells and demonstrated its potential as a comprehensive therapeutic approach for breast cancer patients with metabolic disorders.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Review
Oncology
Laura Guarnaccia, Giovanni Marfia, Matteo Maria Masseroli, Stefania Elena Navone, Melissa Balsamo, Manuela Caroli, Silvia Valtorta, Rosa Maria Moresco, Rolando Campanella, Emanuele Garzia, Laura Riboni, Marco Locatelli
Summary: Glioblastoma is a highly aggressive primary brain tumor with poor prognosis. Angiogenesis plays a crucial role in glioblastoma development and is a potential target for therapy. Metformin, commonly used for type 2 diabetes, has shown promising anti-angiogenic effects in glioblastoma. This review aims to summarize and discuss the potential anti-cancer efficacy of metformin as an add-on therapy for glioblastoma.
Article
Biochemistry & Molecular Biology
Thi Yen Ly Huynh, Ilona Oscilowska, Lukasz Szoka, Ewelina Piktel, Weronika Baszanowska, Katarzyna Bielawska, Robert Bucki, Wojciech Miltyk, Jerzy Palka
Summary: The effect of metformin (MET) on PRODH/POX-dependent apoptosis was studied in wild-type MCF-7 cells and POX knockdown MCF-7 cells. MET was found to increase prolidase activity and decrease collagen biosynthesis, resulting in an increase in substrate concentration for PRODH/POX-dependent ROS formation and caspases activation.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Review
Oncology
Maria Gemelli, Douglas M. Noonan, Valentina Carlini, Giuseppe Pelosi, Massimo Barberis, Riccardo Ricotta, Adriana Albini
Summary: Immune checkpoint inhibitors have been widely used in the treatment of non-small cell lung cancer, but not all patients benefit from them. Other cells in the tumor microenvironment, such as NK cells, also play a role and may affect the response to immune checkpoint inhibitors. Further research is needed to understand the role of pro-inflammatory NK cells in NSCLC and their impact on treatment response to ICIs.
FRONTIERS IN ONCOLOGY
(2022)
Article
Cell Biology
Laura Carpen, Paolo Falvo, Stefania Orecchioni, Giulia Mitola, Roman Hillje, Saveria Mazzara, Patrizia Mancuso, Stefano Pileri, Alessandro Raveane, Francesco Bertolini
Summary: Breast cancer is the most common malignancy in women worldwide and current treatment options depend on histological type, molecular markers, and clinical aggressiveness. Immunotherapy has shown synergistic clinical activity with chemotherapy in triple negative breast cancer. This study used single-cell RNA sequencing technology to assess the immune landscape in two TNBC mouse models, identifying changes in immune cells under different treatment conditions, providing new insights for the diagnosis and treatment of breast cancer.
CELL DEATH DISCOVERY
(2022)
Article
Oncology
Adriana Albini
CANCER PREVENTION RESEARCH
(2022)
Review
Biochemistry & Molecular Biology
Antonino Bruno, Douglas M. Noonan, Roberto Valli, Giovanni Porta, Roberto Taramelli, Lorenzo Mortara, Francesco Acquati
Summary: Ovarian cancer is a malignant gynecological cancer with a 5-year survival rate of 25-30% in the last decade. Cancer immunotherapy is considered a promising strategy for ovarian cancer treatment. The human RNASET2 gene plays a crucial role in suppressing tumor diversity by establishing functional communication between ovarian cancer cells and innate immune system effectors. The protein product of RNASET2 promotes the recruitment of anti-tumoral macrophages to the cancer tissue. This finding suggests the potential of developing a multitasking therapeutic approach for ovarian cancer treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Maria Bellenghi, Giovanna Talarico, Laura Botti, Rossella Puglisi, Claudio Tabolacci, Paola Portararo, Annamaria Piva, Giada Pontecorvi, Alessandra Care, Mario P. Colombo, Gianfranco Mattia, Sabina Sangaletti
Summary: Dysregulated fatty acid metabolism interacts with oncogenic signals, worsening tumor aggressiveness. Overexpression of SCD5 gene reduces SPARC secretion, leading to decreased aggressiveness and reversal of Epithelial to Mesenchymal Transition (EMT) status in the metastatic clone of 4T1.
Article
Biochemistry & Molecular Biology
Clementina Sansone, Luigi Pistelli, Angelo Del Mondo, Luana Calabrone, Angelo Fontana, Douglas M. Noonan, Adriana Albini, Christophe Brunet
Summary: This study demonstrates the anti-inflammatory effects of Diatoxanthin (Dt) on human lung cells, specifically the A549-hACE2 cell line. Dt enhances cell metabolism and ACE2 enzymatic activity, while decreasing the production of interleukin-6 and increasing the release of interleukin-10 in response to the SARS-CoV-2 spike glycoprotein. Dt also upregulates genes and proteins related to the interferon pathway and innate immunity response. These findings suggest that Dt may be a promising therapeutic agent for the treatment and/or prevention of severe inflammatory syndrome associated with SARS-CoV-2 infection.
Article
Medicine, General & Internal
Stefania Orecchioni, Paolo Falvo, Giovanna Talarico, Giulia Mitola, Giulia Bravetti, Patrizia Mancuso, Paola Nicoli, Francesco Bertolini
Summary: In this study, we demonstrated the effectiveness of a triple therapy consisting of cyclophosphamide, vinorelbine, and anti-PD-1 in controlling a highly aggressive, anti-PD-1 resistant model of B-cell non-Hodgkin's lymphoma. This therapy was able to generate an immune memory that effectively controlled tumor re-challenge, even at high inoculum doses. Furthermore, the triple therapy reshaped the immune cell landscape and reduced exhausted T cells in treated mice.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Oncology
Margherita Cortini, Francesca Macchi, Francesca Reggiani, Emanuele Vitale, Maria Veronica Lipreri, Francesca Perut, Alessia Ciarrocchi, Nicola Baldini, Sofia Avnet
Summary: The pathogenesis of osteosarcoma relies on complex interactions between cancer cells and extracellular matrix (ECM) proteins. Understanding these interactions and ECM composition is important for predicting cancer response to chemotherapy and identifying alternative therapeutic targets. This study aims to generate a 3D model that mimics the tumor microenvironment and investigate the role of ECM deposition in chemotherapy response. The findings suggest that targeting ECM proteins may improve outcomes for chemoresistant tumors.
Article
Cell Biology
Luana Calabrone, Valentina Carlini, Douglas M. M. Noonan, Marco Festa, Cinzia Ferrario, Danilo Morelli, Debora Macis, Angelo Fontana, Luigi Pistelli, Christophe Brunet, Clementina Sansone, Adriana Albini
Summary: The exploration of natural preventive molecules from marine microorganisms for nutraceutical and pharmaceutical use has increased. In this study, an extract from the marine diatom Skeletonema marinoi and its carotenoid pigment fucoxanthin showed potential chemopreventive and anti-angiogenic activities against prostate cancer and endothelial cells. The extract and fucoxanthin inhibited cell growth and hindered vascular network formation. Molecular analysis revealed modulations in angiogenesis and inflammation molecules. These findings highlight the potential of microalgae-derived drugs as a source of novel nutraceuticals for cancer prevention.
Article
Oncology
Giulia Bravetti, Paolo Falvo, Giovanna Talarico, Stefania Orecchioni, Francesco Bertolini
Summary: Chemotherapeutic agents have varying effects on cancer, stroma, and immune cells depending on dosage and schedule. Continuous administration at low dosage (metronomic) can activate antigen presenting cells and generate new T cell clones, enhancing immunotherapies. Ongoing clinical trials will confirm or dismiss this hypothesis and provide biomarker data for patient selection.
Article
Biochemistry & Molecular Biology
F. Torricelli, B. Donati, F. Reggiani, V Manicardi, S. Piana, R. Valli, F. Lococo, Alessia Ciarrocchi
Summary: A high-dimensional transcriptomic approach was used to study the morphological evolution of malignant pleural mesothelioma (MPM), revealing the existence of a complex circular ecosystem where MPM and immune cells interact to support S-transdifferentiation. The study also found that TGFB1-polarized M2-tumor associated macrophages promote immune evasion and that TGFB1 expression is correlated with reduced survival probability.
Article
Biochemistry & Molecular Biology
Eugenia Lorenzini, Federica Torricelli, Raffaella Zamponi, Benedetta Donati, Veronica Manicardi, Elisabetta Sauta, Italo Faria do Valle, Francesca Reggiani, Mila Gugnoni, Gloria Manzotti, Valentina Fragliasso, Emanuele Vitale, Simonetta Piana, Valentina Sancisi, Alessia Ciarrocchi
Summary: A study on malignant pleural mesothelioma (MPM) identified a new non-genetic dependency gene, KAP1, which plays a crucial role in cell growth and mitosis execution. By targeting the transcriptional function of KAP1, MPM cell viability can be significantly reduced.
Article
Cardiac & Cardiovascular Systems
Nadia Benedetto, Luana Calabrone, Karolina Gutmanska, Nicoletta Macri, Maria Grazia Cerrito, Riccardo Ricotta, Giuseppe Pelosi, Antonino Bruno, Douglas M. Noonan, Adriana Albini
Summary: This study investigated the cooperation between polyphenol-rich extract from olive mill wastewater (OMWW) and chemotherapy in breast cancer cells, revealing its cardiovascular protective effects and enhancing the efficacy of breast cancer chemotherapy.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)