Article
Pharmacology & Pharmacy
Donglei Sun, Tianhe Zhao, Keyan Long, Mei Wu, Zunzhen Zhang
Summary: Triclosan downregulates FASN expression through upregulating miRNAs, leading to inhibition of lipid metabolism and cell growth in human hepatoma cells via apoptosis.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Jovana Jovankic, Danijela D. Nikodijevic, Milena G. Milutinovic, Aleksandra G. Nikezic, Vesna V. Kojic, Aleksandar M. Cvetkovic, Danijela M. Cvetkovic
Summary: Breast cancer, the second leading cause of death worldwide, has prompted research into non-standard drugs for suppressing its progression. The anti-obesity drug Orlistat has shown significant effects on cancer cell metabolism, such as antiproliferative, proapoptotic, antiangiogenic, antimetastatic, and hypolipidemic effects. Evaluations of Orlistat's anticancer potential in breast cancer cells MDA-MB-231, MDA-MB-468, and MCF-7 showed significant cytotoxic, proapoptotic, and anti-angiogenic effects, while having no significant cytotoxic effects on normal cells. Orlistat also affected lipid levels and redox status parameters, and suppressed genes and proteins involved in fatty acid synthesis, making it a promising supplement for antiangiogenic therapy against breast cancer without side effects.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Cell Biology
Qiqiao Du, Pan Liu, Chunyu Zhang, Tianyu Liu, Wei Wang, Chunliang Shang, Jieyu Wu, Yuandong Liao, Yili Chen, Jiaming Huang, Hao Tan, Yunhe Zhao, Meng Xia, Junxiu Liu, Shuzhong Yao
Summary: This study uncovers a novel molecular mechanism in lymph node metastasis (LNM) of cervical cancer (CC) and identifies fatty acid synthase (FASN) as a crucial player and a potential therapeutic target for LNM in CC.
CELL DEATH & DISEASE
(2022)
Article
Biochemistry & Molecular Biology
Hiromi Sato, Shintaro Narita, Masanori Ishida, Yoshiko Takahashi, Huang Mingguo, Soki Kashima, Ryohei Yamamoto, Atsushi Koizumi, Taketoshi Nara, Kazuyuki Numakura, Mitsuru Saito, Toshiaki Yoshioka, Tomonori Habuchi
Summary: A diet rich in lard increases the risk of prostate cancer development and progression. Two mouse models fed with lard-enriched diets showed enhanced prostate cancer progression and weight gain compared to a fish oil diet. The composition of gut microbiota differed significantly between the two diets, with changes in bacterial species such as Clostridiales and Lactobacillales. The proportion of Lactobacillales in the gut was negatively associated with weight gain and prostate cancer progression. The study also identified genes involved in lipid metabolism and cholesterol biosynthesis that correlated with the abundance of Lactobacillales in the gut.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Genetics & Heredity
Xiaodong Lu, Ka-wing Fong, Fang Wang, Galina Gritsina, Sylvan C. Baca, Jacob E. Berchuck, Jenny Ross, Eva Corey, Navdeep Chandel, William J. Catalona, Ximing Yang, Matthew L. Freedman, Jonathan C. Zhao, Jindan Yu, Lourdes T. Brea, Sandor Spisak, CoIm Morrissey
Summary: The study reveals that HOXB13 suppresses lipogenic transcriptional program in prostate cancer through HDAC3 recruitment, which inhibits tumor metastasis. Loss or mutation of HOXB13 leads to lipid accumulation in PCa cells, promoting cell motility and tumor metastasis. This study provides important insights into the roles of HOXB13 in prostate cancer progression and metastasis.
Review
Oncology
Fahim Ahmad, Murali Krishna Cherukuri, Peter L. Choyke
Summary: While low-risk localized prostate cancer has a good prognosis with effective treatments, metastatic prostate cancer remains incurable and treatment resistance is a major issue. Resistance is primarily driven by tumor heterogeneity, altered genetic signatures, and metabolic reprogramming enabling tumors to adapt to drugs. Understanding prostate cancer metabolism may offer insights into therapy-induced adaptive responses and more durable therapeutic outcomes.
BRITISH JOURNAL OF CANCER
(2021)
Article
Pathology
Henrique J. Cardoso, Marilia I. Figueira, Tiago M. A. Carvalho, Catarina D. M. Serra, Catia V. Vaz, Patricia A. Madureira, Silvia Socorro
Summary: The study found that androgens can change the lipid metabolism of PCa cells and interact with LDL-cholesterol, increasing the viability, proliferation, and migration of PCa cells. These results support clinical data linking obesity with PCa and implicate androgens in this relationship for the first time. Therefore, pharmacological approaches targeting both cholesterol availability and androgens signaling simultaneously are of great significance.
PATHOLOGY RESEARCH AND PRACTICE
(2022)
Article
Cell Biology
Wenting Dai, Zhichao Wang, Guan Wang, Qiong A. Wang, Ralph DeBerardinis, Lei Jiang
Summary: Fatty acid synthase is essential for lipogenesis in cancer cells, but anchorage-independent malignant cells can enhance their redox capacity through reductive carboxylation.
Article
Plant Sciences
Yang Xu, Shrikaar Kambhampati, Stewart A. Morley, Ron Cook, John Froehlich, Doug K. Allen, Christoph Benning
Summary: The study found that ACP4 and RBL10 can affect chloroplast lipid biosynthesis by modulating substrate precursor pools, thus participating in chloroplast lipid assembly and monogalactosyldiacylglycerol biosynthesis. This study shows that Arabidopsis ACP4 and RBL10 independently affect chloroplast membrane lipid biosynthesis.
Article
Food Science & Technology
Sucheewin Krobthong, Yodying Yingchutrakul, Patompon Wongtrakoongate, Hathaichanok Chuntakaruk, Thanyada Rungrotmongkol, Chartchai Chaichana, Thanisorn Mahatnirunkul, Thitikorn Chomtong, Kiattawee Choowongkomon, Chanat Aonbangkhen
Summary: Obesity is a global health concern that can be prevented by physical activities and consuming nutrient-rich functional foods. In this study, nano-liposomal encapsulated bioactive peptides (BPs) were developed to reduce cellular lipids. The nano-liposomal BPs showed potential as functional food ingredients for preventing obesity.
Article
Cell Biology
Ying Yang, Jiaxing He, Bo Zhang, Zhansheng Zhang, Guozhan Jia, Shiqi Liu, Tao Wu, Xianli He, Nan Wang
Summary: SLC25A1 is significantly upregulated in CRC, associated with poor survival in patients, and reprograms energy metabolism through two mechanisms to promote CRC growth. It serves as a potential diagnostic marker and therapeutic target in CRC.
CELL DEATH & DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Yan Song, Fengming Gu, Zhixiang Liu, Zongnan Li, Fu'an Wu, Sheng Sheng
Summary: In this study, two FAS genes were identified in Spodoptera litura, and silencing SlFAS1 was found to significantly affect lipogenesis pathway and metamorphic development in this insect.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Food Science & Technology
Yujie Wang, Haitao Pan, Dian Chen, Dandan Guo, Xingya Wang
Summary: EGCG can inhibit the viability of colorectal cancer cells by regulating fatty acid and energy metabolisms, leading to decreased lipid droplet formation and triglyceride contents.
JOURNAL OF FUNCTIONAL FOODS
(2021)
Article
Pharmacology & Pharmacy
Given Lee, Sifei Han, Zijun Lu, Jiwon Hong, Anthony R. J. Phillips, John A. Windsor, Christopher J. H. Porter, Natalie L. Trevaskis
Summary: Orlistat is a pancreatic lipase inhibitor used to treat obesity by inhibiting dietary lipid absorption. Improved absorption could potentially treat other diseases as well.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2021)
Article
Cell Biology
Zelong Han, Ming Liu, Yuxin Xie, Kunlin Zeng, Ziling Zhan, Yanwen Chen, Li Wang, Xiaoxia Chen, Yaxin Luo, Yu Zeng, Hongchao Zhan, Yingzhuo Lin, Keqin Zhang, Xiaoxia Zhu, Side Liu, Xiaobei Luo, Aidong Zhou
Summary: This study reveals the role of ROS in regulating lipid synthesis during colorectal tumorigenesis through a p53-dependent mechanism. The USP22-FASN axis is identified as an important pathway in this process, and targeting this axis may represent a potential strategy for the treatment of colorectal cancer.
CELL DEATH DISCOVERY
(2022)
Article
Gastroenterology & Hepatology
Alexander Laemmle, Martin Poms, Bernadette Hsu, Mariia Borsuk, Veronique Rufenacht, Joshua Robinson, Martin C. Sadowski, Jean-Marc Nuoffer, Johannes Haberle, Holger Willenbring
Summary: The study identified the critical role of AQP9 in functional urea metabolism and successfully established an in vitro liver disease model of OTCD using hiPSC-Heps. By manipulating hiPSC-Heps, OTC activity and ureagenesis could be corrected, potentially improving the therapy of OTCD through genotype/phenotype correlation and drug screens.
Review
Biochemistry & Molecular Biology
Jianying Han, Xueting Liu, Lixin Zhang, Ronald J. Quinn, Yunjiang Feng
Summary: Tuberculosis remains a major global disease with high mortality and morbidity, posing challenges for drug discovery due to drug resistance and long treatment duration. Recent advances in research on anti-TB natural products and their potential molecular targets have provided new insights and may contribute to accelerating TB drug discovery.
NATURAL PRODUCT REPORTS
(2022)
Article
Chemistry, Multidisciplinary
Miaomiao Liu, Dene R. Littler, Jamie Rossjohn, Ronald J. Quinn
Summary: The study identified a plant-derived ent-kaurane natural product, oridonin (1), and its clinical analogue, HAO472 (2), as compounds that selectively bind to the Nsp9 protein of SARS-CoV-2 and human coronavirus 229E.
Article
Biochemistry & Molecular Biology
Reuben S. E. Young, Andrew P. Bowman, Kaylyn D. Tousignant, Berwyck L. J. Poad, Jennifer H. Gunter, Lisa K. Philp, Colleen C. Nelson, Shane R. Ellis, Ron M. A. Heeren, Martin C. Sadowski, Stephen J. Blanksby
Summary: The demands of cellular energy and biomass in cancer cells affect the metabolic fate of extracellular fatty acids (FAs) and de novo synthesized FAs. This study reveals that FAs from different sources have distinct metabolic fates, which can induce structural changes in cellular lipids and alter signaling behaviors. These findings provide new insights into the complex dynamics of FA metabolism in cancer.
JOURNAL OF LIPID RESEARCH
(2022)
Article
Cell Biology
Kristina Seiler, Magali Humbert, Petra Minder, Iris Mashimo, Anna M. Schlafli, Deborah Krauer, Elena A. Federzoni, Bich Vu, James J. Moresco, John R. Yates, Martin C. Sadowski, Ramin Radpour, Thomas Kaufmann, Jean-Emmanuel Sarry, Joern Dengjel, Mario P. Tschan, Bruce E. Torbett
Summary: This study found that HK3 is dispensable for glycolytic activity in AML cells while promoting cell survival, possibly through direct interaction with the BH3-only protein BIM during ATRA-induced neutrophil differentiation.
CELL DEATH & DISEASE
(2022)
Article
Cell Biology
Daming Zuo, Yu Chen, Jian-piao Cai, Hao-Yang Yuan, Jun-Qi Wu, Yue Yin, Jing-Wen Xie, Jing-Min Lin, Jia Luo, Yang Feng, Long-Jiao Ge, Jia Zhou, Ronald J. Quinn, San-Jun Zhao, Xing Tong, Dong-Yan Jin, Shuofeng Yuan, Shao-Xing Dai, Min Xu
Summary: The twenty-first century has witnessed more than ten major epidemics or pandemics, including the devastating COVID-19. There is an urgent need for novel antiviral drugs with broad-spectrum coverage. This study reports a new broad-spectrum antiviral compound called PAC5. Oral administration of PAC5 was found to eliminate HBV cccDNA and reduce antigen load in mouse models of HBV infection. Additionally, PAC5 significantly decreased viral loads and attenuated lung inflammation in a hamster model of SARS-CoV-2 omicron (BA.1) infection. The mechanism behind these effects involves activation of hnRNPA2B1 and the TBK1-IRF3 pathway, leading to the production of antiviral type I IFNs. These findings suggest that PAC5 could be a promising option for dealing with emerging infectious diseases.
Article
Engineering, Biomedical
Agathe Bessot, Jennifer Gunter, David Waugh, Judith A. Clements, Dietmar W. Hutmacher, Jacqui McGovern, Nathalie Bock
Summary: Increasing evidence highlights the important role of bone marrow adipocytes in prostate cancer bone metastases. However, lack of relevant models has hindered the understanding of human BM-adipocyte effects in this microenvironment. This study combines tunable GelMA-based hydrogels with biomimetic culture of human cells to engineer human bone tumor microenvironments containing BM-adipocytes. In vitro culture of human osteoprogenitors, adipocytes, and PCa cells in GelMA hydrogels leads to the formation of mineralized, adipose, and PCa tumor 3D microtissues, respectively. The stiffness of hydrogels regulates osteoblast mineralization and tumor spheroid formation, while coculture with tumor cells induces morphological changes and delipidation in BM-adipocytes. The in vivo model successfully forms a humanized fatty bone microenvironment and demonstrates that adipocytes support early bone tumor growth. This advanced platform combines natural aspects of the microenvironment with tunable properties for bone tumor research.
ADVANCED HEALTHCARE MATERIALS
(2023)
Article
Chemistry, Medicinal
Yushu Gu, Miaomiao Liu, Bart L. Staker, Garry W. Buchko, Ronald J. Quinn
Summary: SARS-CoV-2 is the pathogen responsible for COVID-19 and the global pandemic. Repurposing clinically approved drugs, gallic acid was identified as a compound that tightly binds to nsp7, a component essential for viral replication. The identification of the gallic acid-binding site may enable the development of a SARS-CoV-2 therapeutic through virtual docking and other strategies.
ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE
(2023)
Article
Oncology
Sugandha Bhatia, Jennifer H. Gunter, Joshua Burgess, Mark N. Adams, Kenneth O'Byrne, Erik W. Thompson, Pascal H. G. Duijf
Summary: Epithelial-mesenchymal plasticity (EMP) is a characteristic of cancer that promotes invasion, metastasis, and therapy resistance. This study shows that non-cancerous human epithelial lung cells can spontaneously shift towards a mesenchymal-like state without genetic changes. This suggests that acquisition of metastasis-associated features may occur prior to genetic alterations and cancerous transformation.
TRANSLATIONAL ONCOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Ka Ho Chow, Ronald J. Quinn, Ian D. Jenkins, Elizabeth H. Krenske
Summary: Oxazolidinones are commonly used as chiral auxiliaries in asymmetric synthesis. The selectivity of removing chiral auxiliaries using different nucleophiles, such as LiOOH, LiOBn, LiSBn, and LiOH, is found to be dependent on the decomposition barrier of the formed intermediates. Mechanistic studies are conducted using DFT calculations to understand the origin of selectivity.
AUSTRALIAN JOURNAL OF CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Yushu Gu, Miaomiao Liu, Bart L. Staker, Garry W. Buchko, Ronald J. Quinn
Summary: SARS-CoV-2 is the cause of COVID-19 and the global pandemic. Repurposing approved drugs can accelerate clinical treatments. Gallic acid was found to bind to the viral protein nsp7, offering potential for SARS-CoV-2 therapeutic development.
ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE
(2023)
Article
Chemistry, Multidisciplinary
Robert J. Young, Sabine L. Flitsch, Michael Grigalunas, Paul D. Leeson, Ronald J. Quinn, Nicholas J. Turner, Herbert Waldmann
Summary: This article reviews the case for focusing on Nature in drug discovery, specifically biomimetic molecules and natural products. It discusses the declining natural product-likeness of licensed drugs and the logic of seeking new bioactive agents with enhanced natural mimicry. The article also explores the potential for computational guidance in designing tailored molecules and emphasizes the advantages of organic/biological structures.
Review
Biochemistry & Molecular Biology
Miaomiao Liu, Alexander P. Martyn, Ronald J. Quinn
Summary: Natural products have the ability to recognize protein surfaces and have advantages in drug delivery. PROTACs, a novel protein degradation approach, have potential applications in the field of natural products. This review summarizes the chemical synthesis and challenges of natural product-based PROTACs, as well as methods for detecting their mechanism of action.
NATURAL PRODUCT REPORTS
(2022)
Article
Oncology
Fernando Souza-Fonseca-Guimaraes, Gustavo R. Rossi, Laura F. Dagley, Momeneh Foroutan, Timothy R. McCulloch, Jumana Yousef, Hae-Young Park, Jennifer H. Gunter, Paul A. Beavis, Cheng-Yu Lin, Soroor Hediyeh-Zadeh, Tania Camilleri, Melissa J. Davis, Nicholas D. Huntington
CANCER IMMUNOLOGY RESEARCH
(2022)