In situ global proteomics profiling of EGCG targets using a cell-permeable and Click-able bioorthogonal probe

Sahadevan, Revathy; Binoy, Anupama; Vechalapu, Sai K.; Nanjan, Pandurangan; Sadhukhan, Sushabhan

doi:10.1016/j.ijbiomac.2023.123991

Cited by 8 publications

(5 citation statements)

References 89 publications

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“…The total radical scavenging capacity of EGCG and MitoEGCG n compounds was measured using the DPPH assay protocol as reported earlier by our group. 16 Briefly, 0.2 mM stock solution of diphenyl picryl radical (DPPH) was prepared in 95% methanol at room temperature in dark. To obtain a final concentration of 0.1–200 μM for the EGCG or MitoEGCG n compounds ( n = 4, 6, or 8), 150 μL of 0.2 mM DPPH solution was added to 50 μL, 4X DMSO stocks of the respective compounds.…”

Section: Methodsmentioning

confidence: 99%

“…The introduction of alkyl groups of different chain lengths was found to increase the stability of EGCG. 16,17,23,24 The alkyl chain will also contribute to the increase in the lipophilicity of the compound and thus, the cellular uptake. Hence, we introduced the TPP moiety at the 4 ′′ position of EGCG via an alkane chain linker anticipating its favorable cellular uptake and mitochondrial targeting.…”

Section: Synthesis and Characterization Of Mitoegcg Nmentioning

confidence: 99%

“…The post-proteomics analysis provided insightful information on the molecular mechanism of action behind the plethoric biological activities exhibited by EGCG. 16 Previously, we have successfully demonstrated that an alkyl substitution at the 4 ′′ -position on the D-ring hydroxyl group can be explored to generate EGCG analogues with increased bioavailability and thus enhanced biological activity. 17,18 The characteristic resonance stabilization of the phenolate at the 4 ′′ -position provides scope for regioselective alkylation at this position.…”

Section: Introductionmentioning

confidence: 99%

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Mitochondria-targeting EGCG derivatives protect H9c2 cardiomyocytes from H₂O₂-induced apoptosis: design, synthesis and biological evaluation

Sahadevan,

Binoy,

Shajan

et al. 2023

RSC Adv.

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Section: Methodsmentioning

confidence: 99%

Section: Synthesis and Characterization Of Mitoegcg Nmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Mitochondria-targeting EGCG derivatives protect H9c2 cardiomyocytes from H₂O₂-induced apoptosis: design, synthesis and biological evaluation

Sahadevan,

Binoy,

Shajan

et al. 2023

RSC Adv.

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“…This means that in the “Warburg effect”, many crucial regulatory enzymes, including hexokinase (HK), phosphofructokinase (PFK), phosphoglycerate mutase-1 (PGAM1), pyruvate kinase (PK), and LDH can be considered as potential targets for antitumor drug development ( 182 ). It has been reported that a novel biological orthogonal probe was used to identify the direct target protein of EGCG based on in situ global proteomics profiling, and subsequent gene ontology analysis revealed these main targets belonged to enzymes regulating pivotal metabolic processes such as glycolysis and energy homeostasis ( 183 ). This investigation declared a unique EGCG interactome and provided an important reference for EGCG to regulate the metabolic process of glycolysis.…”

Section: Regulatory Roles In Tumor Metabolic Reprogrammingmentioning

confidence: 99%

The roles of epigallocatechin gallate in the tumor microenvironment, metabolic reprogramming, and immunotherapy

Li,

Cao,

Sun

et al. 2024

Front. Immunol.

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Cancer, a disease that modern medicine has not fully understood and conquered, with its high incidence and mortality, deprives countless patients of health and even life. According to global cancer statistics, there were an estimated 19.3 million new cancer cases and nearly 10 million cancer deaths in 2020, with the age-standardized incidence and mortality rates of 201.0 and 100.7 per 100,000, respectively. Although remarkable advancements have been made in therapeutic strategies recently, the overall prognosis of cancer patients remains not optimistic. Consequently, there are still many severe challenges to be faced and difficult problems to be solved in cancer therapy today. Epigallocatechin gallate (EGCG), a natural polyphenol extracted from tea leaves, has received much attention for its antitumor effects. Accumulating investigations have confirmed that EGCG can inhibit tumorigenesis and progression by triggering apoptosis, suppressing proliferation, invasion, and migration, altering tumor epigenetic modification, and overcoming chemotherapy resistance. Nevertheless, its regulatory roles and biomolecular mechanisms in the immune microenvironment, metabolic microenvironment, and immunotherapy remain obscure. In this article, we summarized the most recent updates about the effects of EGCG on tumor microenvironment (TME), metabolic reprogramming, and anti-cancer immunotherapy. The results demonstrated EGCG can promote the anti-cancer immune response of cytotoxic lymphocytes and dendritic cells (DCs), attenuate the immunosuppression of myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs), and inhibit the tumor-promoting functions of tumor-associated macrophages (TAMs), tumor-associated neutrophils (TANs), and various stromal cells including cancer-associated fibroblasts (CAFs), endothelial cells (ECs), stellate cells, and mesenchymal stem/stromal cells (MSCs). Additionally, EGCG can suppress multiple metabolic reprogramming pathways, including glucose uptake, aerobic glycolysis, glutamine metabolism, fatty acid anabolism, and nucleotide synthesis. Finally, EGCG, as an immunomodulator and immune checkpoint blockade, can enhance immunotherapeutic efficacy and may be a promising candidate for antitumor immunotherapy. In conclusion, EGCG plays versatile regulatory roles in TME and metabolic reprogramming, which provides novel insights and combined therapeutic strategies for cancer immunotherapy.

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“…(−)-Epigallocatechin-3- O -gallate (EGCG), a major green tea polyphenol and therapeutically active compound known to elicit health-beneficial activities against diseases, including cancer. − EGCG exhibits its anticancer activity by regulating various signaling pathways associated with cancer progression . However, low bioavailability, poor stability, , and less membrane permeability minimize the use of EGCG as a therapeutic agent. , To overcome these shortcomings, various structural derivatizations of EGCG have been carried out to enhance its biological activities .…”

Section: Introductionmentioning

confidence: 99%

4″-Alkyl EGCG Derivatives Induce Cytoprotective Autophagy Response by Inhibiting EGFR in Glioblastoma Cells

Singh,

Ghosh,

Roy

et al. 2024

ACS Omega

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Epidermal growth factor receptor (EGFR)-targeted therapy has been proven vital in the last two decades for the treatment of multiple cancer types, including nonsmall cell lung cancer, glioblastoma, breast cancer and head and neck squamous cell carcinoma. Unfortunately, the majority of approved EGFR inhibitors fall into the drug resistance category because of continuous mutations and acquired resistance. Recently, autophagy has surfaced as one of the emerging underlying mechanisms behind resistance to EGFR-tyrosine kinase inhibitors (TKIs). Previously, we developed a series of 4″-alkyl EGCG (4″-C n EGCG, n = 6, 8, 10, 12, 14, 16, and 18) derivatives with enhanced anticancer effects and stability. Therefore, the current study hypothesized that 4″-alkyl EGCG might induce cytoprotective autophagy upon EGFR inhibition, and inhibition of autophagy may lead to improved cytotoxicity. In this study, we have observed growth inhibition and caspase-3-dependent apoptosis in 4″-alkyl EGCG derivativetreated glioblastoma cells (U87-MG). We also confirmed that 4″-alkyl EGCG could inhibit EGFR in the cells, as well as mutant L858R/T790M EGFR, through an in vitro kinase assay. Furthermore, we have found that EGFR inhibition with 4″-alkyl EGCG induces cytoprotective autophagic responses, accompanied by the blockage of the AKT/mTOR signaling pathway. In addition, cytotoxicity caused by 4″-C 10 EGCG, 4″-C 12 EGCG, and 4″-C 14 EGCG was significantly increased after the inhibition of autophagy by the pharmacological inhibitor chloroquine. These findings enhance our understanding of the autophagic response toward EGFR inhibitors in glioblastoma cells and suggest a potent combinatorial strategy to increase the therapeutic effectiveness of EGFR-TKIs.

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In situ global proteomics profiling of EGCG targets using a cell-permeable and Click-able bioorthogonal probe

Cited by 8 publications

References 89 publications

Mitochondria-targeting EGCG derivatives protect H9c2 cardiomyocytes from H₂O₂-induced apoptosis: design, synthesis and biological evaluation

Mitochondria-targeting EGCG derivatives protect H9c2 cardiomyocytes from H₂O₂-induced apoptosis: design, synthesis and biological evaluation

The roles of epigallocatechin gallate in the tumor microenvironment, metabolic reprogramming, and immunotherapy

4″-Alkyl EGCG Derivatives Induce Cytoprotective Autophagy Response by Inhibiting EGFR in Glioblastoma Cells

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In situ global proteomics profiling of EGCG targets using a cell-permeable and Click-able bioorthogonal probe

Cited by 8 publications

References 89 publications

Mitochondria-targeting EGCG derivatives protect H9c2 cardiomyocytes from H2O2-induced apoptosis: design, synthesis and biological evaluation

Mitochondria-targeting EGCG derivatives protect H9c2 cardiomyocytes from H2O2-induced apoptosis: design, synthesis and biological evaluation

The roles of epigallocatechin gallate in the tumor microenvironment, metabolic reprogramming, and immunotherapy

4″-Alkyl EGCG Derivatives Induce Cytoprotective Autophagy Response by Inhibiting EGFR in Glioblastoma Cells

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Mitochondria-targeting EGCG derivatives protect H9c2 cardiomyocytes from H₂O₂-induced apoptosis: design, synthesis and biological evaluation

Mitochondria-targeting EGCG derivatives protect H9c2 cardiomyocytes from H₂O₂-induced apoptosis: design, synthesis and biological evaluation