Review
Oncology
Enyu Tang, Siyang Liu, Zhiming Zhang, Rixin Zhang, Dejing Huang, Tong Gao, Tianze Zhang, Guangquan Xu
Summary: This study aims to explore the role of the glutamine pathway in the metabolism of lung cancer and its potential therapeutic value.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biochemical Research Methods
Thambi Dorai, John T. Pinto, Travis T. Denton, Boris F. Krasnikov, Arthur J. L. Cooper
Summary: This article discusses the importance of the glutaminase II pathway in cancer cell metabolism, particularly as a mechanism for providing carbon sources. Studies suggest that inhibiting GLS1 alone does not prevent the glutaminase II pathway from supplying carbon derived from glutamine, highlighting the potential therapeutic efficacy of specific inhibitors for omega-amidase in combination with GLS1 inhibitors.
ANALYTICAL BIOCHEMISTRY
(2022)
Article
Medicine, Research & Experimental
Hsiu-Wen Tsai, Ioan Lina, Kevin M. Motz, Liam Chung, Dacheng Ding, Michael K. Murphy, Michael Feeley, Jennifer H. Elisseeff, Alexander T. Hillel
Summary: The study demonstrates that broadly active glutamine antagonist DON significantly reduces fibrosis in iLTS mice. These results suggest that glutamine inhibition may be a therapeutic option to reduce fibrosis in laryngotracheal stenosis.
Review
Biology
Arthur J. L. Cooper, Thambi Dorai, John T. Pinto, Travis T. Denton
Summary: Many types of cancer cells rely on L-glutamine to meet their metabolic demands. This review highlights the metabolic importance of the GT omega A pathway in cancer cells and proposes that targeting L-glutamine metabolism requires consideration of both the canonical and GT omega A pathways. L-glutamine is a major energy source for many cancers.
Article
Chemistry, Medicinal
Xiujin Chang, Min Wang, Di Zhang, Yuqing Zhang, Jubo Wang, Zhiyu Li, Jinlei Bian, Xi Xu
Summary: Tumor cells undergo metabolic reprogramming to support their rapid growth and proliferation. A novel series of GLS1 allosteric inhibitors were designed and synthesized using structure-based drug design approaches. Compound LWG-301 exhibited moderate antitumor effects by blocking glutamine metabolism and inducing apoptosis. This paper provides valuable insights and a new design strategy for the development of GLS1 allosteric inhibitors.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Ziyi Mai, Jing Zhong, Jiasi Zhang, Guimei Chen, Yan Tang, Wen Ma, Guang Li, Zhenzhen Feng, Fangzhou Li, Xing-Jie Liang, Yuanyuan Yang, Zhiqiang Yu
Summary: The carrier-free immunotherapeutic nanobooster C9SN, constructed by the self-assembly of glutaminase inhibitor compound 968 (C968) and photosensitizer Chlorin e6, enhances the immunotherapeutic effect of photo-dynamic therapy (PDT) by preventing glutamine metabolism and amplifying intracellular oxidative stress. It also remodels the tumor microenvironment and activates cytotoxic T lymphocytes to suppress tumor growth.
Article
Chemistry, Medicinal
Xi Xu, Xiujin Chang, Jingxuan Huang, Di Zhang, Min Wang, Tian Jing, Yu Zhuang, Junping Kou, Zhixia Qiu, Jubo Wang, Zhiyu Li, Jinlei Bian
Summary: A promising GLS1 allosteric inhibitor 41e with strong binding affinity, superior metabolic stability, and moderate anti-tumor activity has been discovered. Mechanistic studies revealed that 41e blocks glutamine metabolism, induces ROS production, and triggers apoptosis in HCT116 cells.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Sabine Ruegenberg, Felix A. M. C. Mayr, Ilian Atanassov, Ulrich Baumann, Martin S. Denzel
Summary: The hexosamine pathway (HP) is a key anabolic pathway that regulates the lifespan of Caenorhabditis elegans. Protein kinase A (PKA) mediates the phosphorylation of GFAT-1 to control its activity and feedback inhibition mechanism.
NATURE COMMUNICATIONS
(2021)
Article
Biotechnology & Applied Microbiology
Jingjing Ge, Baohong Wang, Shuai Zhao, Jiaju Xu
Summary: NEAT1 is highly expressed in medulloblastoma and promotes upregulation of glutamine metabolism in cisplatin-resistant cells. NEAT1 acts as a ceRNA of miR-23a-3p to downregulate its expression. miR-23a-3p is significantly downregulated in MB patient tissues and cisplatin-resistant MB cells.
Article
Biochemistry & Molecular Biology
Shams Tabrez, Torki A. Zughaibi, Mehboob Hoque, Mohd Suhail, Mohammad Imran Khan, Azhar U. Khan
Summary: In this study, 12 potent compounds were identified from a traditional Chinese medicine database as potential GLS inhibitors. Among them, ZINC03978829 and ZINC32296657 exhibited higher binding energy values with GLS. Molecular dynamics simulations confirmed that these compounds form stable complexes with GLS, suggesting their potential as therapeutic agents against cancer. Further laboratory testing is required to optimize these compounds as GLS inhibitors.
Article
Oncology
Ji Hye Kim, Jinyoung Lee, Young-Ra Cho, So-Yeon Lee, Gi-Jun Sung, Dong-Myung Shin, Kyung-Chul Choi, Jaekyoung Son
Summary: Pancreatic cancer is a deadly tumor with poor prognosis, often detected in advanced stages. TFEB expression in pancreatic cancer cells plays a crucial role in regulating glutaminase-mediated glutamine metabolism, suggesting it as a potential new target for therapy.
Article
Oncology
Juan De los Santos-Jimenez, Tracy Rosales, Bookyung Ko, Jose A. Campos-Sandoval, Francisco J. Alonso, Javier Marquez, Ralph J. DeBerardinis, Jose M. Mates
Summary: Using the GLS inhibitor CB-839, we observed significant changes in glutamine metabolism in three glioblastoma cell lines, including alterations in the tricarboxylic acid cycle and nucleotide biosynthesis pathways. The T98G cell line showed the most pronounced metabolite level modifications and increased levels of acetylated and methylated metabolites. CB-839 treatment also resulted in decreased levels of pyrimidine biosynthesis metabolites and accumulation of intermediate metabolites in the de novo purine nucleotide biosynthesis pathway. These findings provide insights for the development of future combination therapies with CB-839.
Article
Biochemistry & Molecular Biology
Federica Barreca, Michele Aventaggiato, Laura Vitiello, Luigi Sansone, Matteo Antonio Russo, Antonello Mai, Sergio Valente, Marco Tafani
Summary: This study suggests that activation of SIRT5 and reduction in Pi could be a valid strategy to inhibit cell proliferation by reducing glutamine metabolism and mitophagy, leading to the accumulation of ROS.
Article
Biochemistry & Molecular Biology
Parash Prasad, Sampurna Ghosh, Sib Sankar Roy
Summary: Glutamine deficiency in the core of tumors can increase the cancer stem cell population, and the combination therapy with MDiVi-1 and L-DON is an effective approach to reduce CSCs population in tumor. The study reveals the association between glutamine deprivation and stemness in cancer cells, highlighting the potential of targeting glutamine metabolism for cancer therapy. The findings suggest that metabolic reprogramming induced by glutamine starvation plays a key role in promoting the stem cell characteristics in tumor cells.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Cardiac & Cardiovascular Systems
Sachiko Yoshikawa, Manabu Nagao, Ryuji Toh, Masakazu Shinohara, Takuya Iino, Yasuhiro Irino, Makoto Nishimori, Hidekazu Tanaka, Seimi Satomi-Kobayashi, Tatsuro Ishida, Ken-Ichi Hirata
Summary: This study demonstrates that increased GLS1 expression and subsequent activation of glutaminolysis are associated with exacerbation of cardiac hypertrophy and fibrosis. Inhibition of GLS1 antagonized adverse cardiac remodeling in vitro and in vivo, partly due to reduction of glutamine-derived metabolites necessary for cellular growth and proliferation. Increased glutamine utilization in cardiac cells may be related to the pathogenesis and development of HF.
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
(2022)
Article
Cell Biology
Tu Nguyen, Brian James Kirsch, Ryoichi Asaka, Karim Nabi, Addison Quinones, Jessica Tan, Marjorie Justine Antonio, Felipe Camelo, Ting Li, Stephanie Nguyen, Giang Hoang, Kiet Nguyen, Sunag Udupa, Christos Sazeides, Yao-An Shen, Amira Elgogary, Juvenal Reyes, Liang Zhao, Andre Kleensang, Kaisorn Lee Chaichana, Thomas Hartung, Michael J. Betenbaugh, Suely K. Marie, Jin G. Jung, Tian-Li Wang, Edward Gabrielson, Anne Le
Article
Geriatrics & Gerontology
Lina Ma, Lolita S. Nidadavolu, Huanle Yang, Jackie Langdon, Reyhan Westbrook, Benjamin M. W. Tsui, Taek-Soo Lee, Jared Hinson, Shizhang Ling, Ruth Marx-Rattner, Yuqiong Wu, Tu Nguyen, Jessica Tan, Mohammed Khadeer, Ruin Moaddel, Anne Le, Jeremy D. Walston, Peter M. Abadir
Summary: Selective knockdown of IL-6 in a frail mouse with chronic inflammation can reverse some changes associated with chronic inflammation, but it also leads to higher mortality.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2021)
Article
Medicine, Research & Experimental
Reyhan Westbrook, Tae Chung, Jacqueline Lovett, Chris Ward, Humberto Joca, Huanle Yang, Mohammed Khadeer, Jing Tian, Qian-Li Xue, Anne Le, Luigi Ferrucci, Ruin Moaddel, Rafa de Cabo, Ahmet Hoke, Jeremy Walston, Peter M. Abadir
Article
Clinical Neurology
Khoa Pham, Micah J. Maxwell, Heather Sweeney, Jesse Alt, Rana Rais, Charles G. Eberhart, Barbara S. Slusher, Eric H. Raabe
Summary: Researchers developed a new compound, JHU395, targeting MYC-expressing medulloblastoma, which significantly inhibited tumor cell growth at lower concentrations and increased apoptosis rates, resulting in extended survival in mice.
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
(2021)
Article
Biochemical Research Methods
Giang Hoang, Cissy Zhang, Nabeel Attarwala, Jin G. Jung, Arthur J. L. Cooper, Anne Le
Summary: Recent metabolomic studies have revealed the existence of metabolic cycles involving glucose-NAAG-glutamate, glutamine-lactate-glucose, and glutamate-GABA-succinate in cancer cells. These cycles play crucial roles in storing carbon sources within oncogenic cells, impacting cell metabolism and potential therapeutic targets.
ANALYTICAL BIOCHEMISTRY
(2021)
Article
Oncology
Rachael E. Maynard, Brad Poore, Allison R. Hanaford, Khoa Pham, Madison James, Jesse Alt, Youngran Park, Barbara S. Slusher, Pablo Tamayo, Jill Mesirov, Tenley C. Archer, Scott L. Pomeroy, Charles G. Eberhart, Eric H. Raabe
Summary: By constructing a neural stem cell model, it was found that the combination of mTOR inhibitors and carboplatin may be an effective therapy for high-risk medulloblastoma.
Review
Biochemistry & Molecular Biology
Yao-An Shen, Chi-Long Chen, Yi-Hsuan Huang, Emily Elizabeth Evans, Chun-Chia Cheng, Ya-Jie Chuang, Cissy Zhang, Anne Le
Summary: Targeting glutamine catabolism for cancer therapy has gained research attention, with focus on inhibiting catalytic enzymes like GLS. However, resistance to treatments targeting glutaminolysis has been observed, leading to the development of combination therapies as a potential solution.
CURRENT OPINION IN CHEMICAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Arianna F. Anzmann, Olivia L. Sniezek, Alexandra Pado, Veronica Busa, Frederic M. Vaz, Simion D. Kreimer, Lauren R. DeVine, Robert N. Cole, Anne Le, Brian J. Kirsch, Steven M. Claypool, Hilary J. Vernon
Summary: In a new HEK293-based tafazzin-deficiency model, complex I (CI) and PARL were found to be altered, leading to decreased levels of specific CI subunits and assembly factor. Remediation of these defects with pharmacologic agents SS-31 and bromoenol lactone enhances understanding of the cardiac pathology of BTHS.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Cell Biology
Tu Nguyen, Mei Zheng, Maura Knapp, Nikola Sladojevic, Qin Zhang, Lizhuo Ai, Devin Harrison, Anna Chen, Albert Sitikov, Le Shen, Frank J. Gonzalez, Qiong Zhao, Yun Fang, James J. K. Liao, Rongxue Wu
Summary: The decline in endothelial ARNT expression contributes to the suppressed angiogenic phenotype in diabetic mice. The cytoprotective effect of ARNT in endothelial cells is partially mediated by declines in ROS production.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Biochemical Research Methods
Shenghao Guo, Cissy Zhang, Anne Le
Summary: Single-cell metabolomics is a powerful tool for high-throughput metabolic analysis at the cellular level, with great potential in decoding cell heterogeneity and identifying cell types within colonies. The development of various equipment and techniques has made SCM analysis possible for a wide range of biological samples, leading to fruitful findings in various fields such as phytology, neurology, and oncology.
CURRENT OPINION IN BIOTECHNOLOGY
(2021)
Article
Oncology
Cissy Zhang, Addison Quinones, Anne Le
Summary: One of the defining features of cancer cells is their ability to reprogram metabolism to meet their needs. Recent research has shown that cancer cells can store vital metabolites for later use, providing new insights into potential cancer treatment strategies.
SEMINARS IN CANCER BIOLOGY
(2022)
Article
Oncology
Khoa Pham, Allison R. Hanaford, Brad A. Poore, Micah J. Maxwell, Heather Sweeney, Akhila Parthasarathy, Jesse Alt, Rana Rais, Barbara S. Slusher, Charles G. Eberhart, Eric H. Raabe
Summary: The oncogene MYC alters cellular metabolism and its amplification in medulloblastoma leads to distinct metabolic characteristics. Comprehensive metabolic profiling of MYC-amplified medulloblastoma revealed an increased reliance on targetable metabolic pathways. However, metabolism of MYC-amplified cell lines differed from in vivo tumor models, indicating the importance of in vivo metabolic analyses. Understanding the metabolic vulnerabilities of MYC-amplified medulloblastoma may inform the development of targeted therapies.
Article
Materials Science, Biomaterials
Cissy Zhang, Giang Hoang, Nabeel Attarwala, Arthur J. L. Cooper, Ryoichi Asaka, Anne Le
Summary: The release of metabolic materials from dead cancer cells post-therapy can promote the growth of surviving cancer cells. The surviving cancer cells take up these metabolites and enhance multiple vital metabolic processes, resulting in significant growth. This phenomenon is observed only in oncogenic cells, providing opportunities for intervention in cancer cell growth.
Article
Geriatrics & Gerontology
Reyhan Westbrook, Cissy Zhang, Huanle Yang, Jing Tian, Shenghao Guo, Qian-Li Xue, Jeremy Walston, Anne Le, Peter M. Abadir
Summary: This study found that dysregulation of energy producing metabolic pathways is associated with frailty in older adults. Elevated levels of TCA cycle and glycolytic intermediates were observed in frail subjects, while the differences in ATP and other energy metabolites between young, nonfrail, and frail adults were not significant. Additionally, serum levels of neurotransmitters were significantly elevated in older adults with frailty.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2022)
