Journal ArticleDOI
Silibinin induces metabolic crisis in triple-negative breast cancer cells by modulating EGFR-MYC-TXNIP axis: potential therapeutic implications.
Mohammad Askandar Iqbal,Shilpi Chattopadhyay,Farid Ahmad Siddiqui,Farid Ahmad Siddiqui,Asad Ur Rehman,Asad Ur Rehman,Shumaila Siddiqui,Gopinath Prakasam,Gopinath Prakasam,Asifa Khan,Sarwat Sultana,Rameshwar N. K. Bamezai +11 more
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TLDR
The results highlight the importance of EGFR‐MYC‐TXNIP axis in regulating TNBC metabolism, demonstrate the anti‐TNBC activity of silibinin, and argue in favor of targeting metabolic vulnerabilities of TNBC, at least in combination with mainstay chemotherapeutic drugs, to effectively treat TNBC patients.Abstract:
Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer with limited treatment modalities and poor prognosis. Metabolic reprogramming in cancer is considered a hallmark of therapeutic relevance. Here, we report disruption of metabolic reprogramming in TNBC cells by silibinin via modulation of EGFR-MYC-TXNIP signaling. Metabolic assays combined with LC-MS-based metabolomics revealed inhibition of glycolysis and other key biosynthetic pathways by silibinin, to induce metabolic catastrophe in TNBC cells. Silibinin-induced metabolic suppression resulted in decreased cell biomass, proliferation, and stem cell properties. Mechanistically, we identify EGFR-MYC-TXNIP as an important regulator of TNBC metabolism and mediator of inhibitory effects of silibinin. Highlighting the clinical relevance of our observations, the analysis of METABRIC dataset revealed deregulation of EGFR-MYC-TXNIP axis in TNBC and association of EGFRhigh -MYChigh -TXNIPlow signature with aggressive glycolytic metabolism and poor disease-specific and metastasis-free survival. Importantly, combination treatment of silibinin or 2-deoxyglucose (glycolysis inhibitor) with paclitaxel synergistically inhibited proliferation of TNBC cells. Together, our results highlight the importance of EGFR-MYC-TXNIP axis in regulating TNBC metabolism, demonstrate the anti-TNBC activity of silibinin, and argue in favor of targeting metabolic vulnerabilities of TNBC, at least in combination with mainstay chemotherapeutic drugs, to effectively treat TNBC patients.read more
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Path of Silibinin from diet to medicine: A dietary polyphenolic flavonoid having potential anti-cancer therapeutic significance.
Hardeep Singh Tuli,Sonam Mittal,Diwakar Aggarwal,Gaurav Parashar,Nidarshana Chaturvedi Parashar,Sushil Kumar Upadhyay,Tushar Singh Barwal,Aklank Jain,Ginpreet Kaur,Raj Savla,Katrin Sak,Manoj Kumar,Mehmet Varol,Ashif Iqubal,Anil K. Sharma +14 more
TL;DR: This extensive review focuses on functional aspects governed by Silibinin in chemopreventive potential and clinical trials that are currently ongoing, at a single platform.
Journal ArticleDOI
TXNIP: A Double-Edged Sword in Disease and Therapeutic Outlook
TL;DR: The main structure, binding proteins, pathways, and the role of TXNIP in diseases are summarized, aiming to explore the double-edged sword role ofTXNIP, and expect it to be helpful for future treatment usingtxNIP as a therapeutic target.
Journal ArticleDOI
Clinical value and potential mechanisms of COL8A1 upregulation in breast cancer: a comprehensive analysis
Wei Peng,Jian-Di Li,Jing-Jing Zeng,Xiao-Ping Zou,Deng Tang,Wei Tang,Minhua Rong,Ying Li,Wen-Bin Dai,Zhong-Qing Tang,Zhen-Bo Feng,Gang Chen +11 more
TL;DR: Elevated COL8A1 may promote the migration of breast cancer by mediating the ECM-receptor interaction and synergistically interplaying with DEGs and its positively related CEGs independently of molecular subtypes.
Journal ArticleDOI
Multiomics integrative analysis reveals antagonistic roles of CBX2 and CBX7 in metabolic reprogramming of breast cancer
Mohammad Askandar Iqbal,Shumaila Siddiqui,Asad Ur Rehman,Farid Ahmad Siddiqui,Farid Ahmad Siddiqui,Prithvi Singh,Bhupender Kumar,Daman Saluja +7 more
TL;DR: In this article, the authors performed pathway-based analysis and identified outstanding roles of CBX2 and CBX7 in positive and negative regulation of glucose metabolism, respectively, using transcriptomic and metabolomic data from breast cancer patients.
Journal ArticleDOI
Metabolomic insights into the mode of action of natural products in the treatment of liver disease
Diren Beyoğlu,Jeffrey R. Idle +1 more
TL;DR: The potential of metabolomics is examined to help answer queries regarding the safety, efficacy, and quality of natural product remedies for liver disease in a western medical context, illustrated by investigations of yin chen hao tang, silymarin, and xiaozhang tie.
References
More filters
Journal ArticleDOI
Hallmarks of cancer: the next generation.
TL;DR: Recognition of the widespread applicability of these concepts will increasingly affect the development of new means to treat human cancer.
Journal ArticleDOI
Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation
TL;DR: It is proposed that the metabolism of cancer cells, and indeed all proliferating cells, is adapted to facilitate the uptake and incorporation of nutrients into the biomass needed to produce a new cell.
Journal ArticleDOI
The cBio Cancer Genomics Portal: An Open Platform for Exploring Multidimensional Cancer Genomics Data
Ethan Cerami,Jianjiong Gao,Ugur Dogrusoz,Benjamin Gross,Selcuk Onur Sumer,Bulent Arman Aksoy,Anders Jacobsen,Caitlin Byrne,Michael Heuer,Erik G. Larsson,Yevgeniy Antipin,Boris Reva,Arthur P. Goldberg,Chris Sander,Nikolaus Schultz +14 more
TL;DR: The cBio Cancer Genomics Portal significantly lowers the barriers between complex genomic data and cancer researchers who want rapid, intuitive, and high-quality access to molecular profiles and clinical attributes from large-scale cancer genomics projects and empowers researchers to translate these rich data sets into biologic insights and clinical applications.
Journal ArticleDOI
Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal
Jianjiong Gao,Bulent Arman Aksoy,Ugur Dogrusoz,Gideon Dresdner,Benjamin Gross,S. Onur Sumer,Yichao Sun,Anders Jacobsen,Rileen Sinha,Erik Larsson,Ethan Cerami,Chris Sander,Nikolaus Schultz +12 more
TL;DR: A practical guide to the analysis and visualization features of the cBioPortal for Cancer Genomics, which makes complex cancer genomics profiles accessible to researchers and clinicians without requiring bioinformatics expertise, thus facilitating biological discoveries.
Journal ArticleDOI
New Colorimetric Cytotoxicity Assay for Anticancer-Drug Screening
Philip Skehan,Ritsa Storeng,Dominic A. Scudiero,Anne Monks,James B. McMahon,David T. Vistica,Jonathan T. Warren,Heidi R. Bokesch,Susan Kenney,Michael R. Boyd +9 more
TL;DR: The SRB assay provides a sensitive measure of drug-induced cytotoxicity, is useful in quantitating clonogenicity, and is well suited to high-volume, automated drug screening.