Abstract:Green tea catechins are bioactive polyphenol compounds which have attracted significant attention for their diverse biological activities and potential health benefits. Notably, epigallocatechin-3-gallate (EGCG) has emerged as a potent apoptosis inducer through mechanisms involving caspase activation, modulation of Bcl-2 family proteins, disruption of survival signaling pathways and by regulating the redox balance, inducing oxidative stress. Furthermore, emerging evidence suggests that green tea catechins can … Show more
“…EGCG has become an important pathway for epigenetic therapy for leukemia and MDS, and it also has synergies when used in combination with conventional chemotherapy drugs (Della Via et al, 2023). In addition, in phase Ⅱ double-blind, placebocontrolled randomized clinical trial, preventive use of EGCG solution significantly reduced the incidence and severity of RID in patients with adjuvant radiotherapy for breast cancer (Zhao et al, 2022).…”
Epigenetic changes are heritable changes in gene expression without changes in the nucleotide sequence of genes. Epigenetic changes play an important role in the development of cancer and in the process of malignancy metastasis. Previous studies have shown that abnormal epigenetic changes can be used as biomarkers for disease status and disease prediction. The reversibility and controllability of epigenetic modification changes also provide new strategies for early disease prevention and treatment. In addition, corresponding drug development has also reached the clinical stage. In this paper, we will discuss the recent progress and application status of tumor epigenetic biomarkers from three perspectives: DNA methylation, non-coding RNA, and histone modification, in order to provide new opportunities for additional tumor research and applications.
“…EGCG has become an important pathway for epigenetic therapy for leukemia and MDS, and it also has synergies when used in combination with conventional chemotherapy drugs (Della Via et al, 2023). In addition, in phase Ⅱ double-blind, placebocontrolled randomized clinical trial, preventive use of EGCG solution significantly reduced the incidence and severity of RID in patients with adjuvant radiotherapy for breast cancer (Zhao et al, 2022).…”
Epigenetic changes are heritable changes in gene expression without changes in the nucleotide sequence of genes. Epigenetic changes play an important role in the development of cancer and in the process of malignancy metastasis. Previous studies have shown that abnormal epigenetic changes can be used as biomarkers for disease status and disease prediction. The reversibility and controllability of epigenetic modification changes also provide new strategies for early disease prevention and treatment. In addition, corresponding drug development has also reached the clinical stage. In this paper, we will discuss the recent progress and application status of tumor epigenetic biomarkers from three perspectives: DNA methylation, non-coding RNA, and histone modification, in order to provide new opportunities for additional tumor research and applications.
“…Originating from China, tea was introduced to the world thousands of years ago via the Silk Road. The production of green tea involves decoction or steaming of freshly harvested leaves to inactivate polyphenol oxidase and other enzymes that prevent fermentation/oxidation, preserving the active chemical properties [ 92 ]. As one of the most consumed beverages worldwide, green tea has been the focus of much research, and its polyphenolic compounds have been shown to have many benefits for human health.…”
Section: Natural Medicines With Therapeutic Potential For Aplmentioning
confidence: 99%
“…Catechins are inexpensive, safe, and can be administered orally. Catechins, especially EGCG, have multifaceted effects that make them attractive candidates for the prevention and treatment of leukemia and myelodysplastic syndrome [ 92 , 93 ]. Fig.…”
Section: Natural Medicines With Therapeutic Potential For Aplmentioning
confidence: 99%
“…Of the four major catechins, EGCG is the most abundant and potent polyphenolic compound in green tea extract, accounting for 50–75% of total catechins [ 92 ]. Due to its long half-life, the compound is rapidly absorbed and distributed in all tissues [ 93 ].…”
Section: Natural Medicines With Therapeutic Potential For Aplmentioning
Acute promyelocytic leukemia (APL), which was once considered one of the deadliest types of leukemia, has become a curable malignancy since the introduction of all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) as clinical treatments. ATO, which has become the first-line therapeutic agent for APL, is derived from the natural mineral product arsenic, exemplifying an important role of natural products in the treatment of APL. Many other natural products, ranging from small-molecule compounds to herbal extracts, have also demonstrated great potential for the treatment and adjuvant therapy of APL. In this review, we summarize the natural products and representative components that have demonstrated biological activity for the treatment of APL. We also discuss future directions in better exploring their medicinal value, which may provide a reference for subsequent new drug development and combination therapy programs.
“…It also been reported that EGCG inhibit the angiogenesis, induce epigenetic modifications, carcinogenesis, and metastasis in animal models (17,18) . Plenty of reports in animals, as well as case-control and epidemiologic studies in humans, reveal that green tea consumption or oral administration for long-term significantly reduces the incidence of various cancers (19,20) , indicated a vital role of EGCG in the chemoprevention of cancer. The large number reports suggested the excellent anticancer potency of EGCG alone as well as along other compounds or drugs, however the specific binding target for EGCG is not been studied extensively.…”
Histone methyltransferases are selectively catalyzing the methylation of lysine or arginine residues of target histone and non-histone proteins, classified as lysine methyltransferases and arginine methyltransferases. The EZH2 and PRMT5 catalyze trimethylation of H3 at K27 and symmetric dimethylation of H4 at R3 respectively. These histone repressive marks have been considered as hallmarks in cancer. Both PRMT5 and EZH2 over expressed in several cancers and have been considered as important target of drug development. As a result, many synthetic molecules as inhibitors of both PRMT5 and EZH2 are at different level of preclinical and clinical phases. Cancer atlas data analysis revealed that both PRMT5 and EZH2 had shown more than 90% amplification in breast cancer alone. We screened an array of phytocompounds towards the inhibition of PRMT5 and EZH2 usingin silico, in vitroassays. Among them Epigallocatechin-3-gallate (EGCG) has interacted with human PRMT5: MEP50 and EZH2 efficiently. The EGCG interacted within the SAM binding site, with a π-cation interaction at Lys 333 and H-bonds with Tyr324, Tyr334, Gly365, Leu437, and Glu444. Surface plasmon resonance analysis revealed that EGCG has strong binding affinity in nanomolar concentrations with both PRMT5-MEP50 than EZH2. Further in vitro methylation and cell-based assays proved the inhibitory potential of EGCG by reducing the catalytic products of PRMT5 and EZH2 i.e., H4R3me2s & H3K27me3 respectively and showed that it induced autophagy and apoptosis. Furthermorein vivo, mouse xenografts studies demonstrated that oral dosage, reduced tumor size significantly with reduction in proliferation marker Ki67 and these histone repressive marks. Finally conclude that inhibition of PRMT5 and EZH2 by EGCG potentially can be used to develop combined therapeutic approaches.
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