{"title":"EGCG和杨梅素对ME180和SiHa细胞系宫颈癌生物标志物的协同抗增殖作用","authors":"Kaviyaprabha Rangaraj, Miji Thandaserry Vasudevan, Suseela Rangaraj, Rachana Kumar, Sridhar Muthusami, Tahani Awad Alahmadi, Arunachalam Chinnathambi, Palanisamy Arulselvan, Chaiyavat Chaiyasut, Muruganantham Bharathi","doi":"10.2174/0115665232363374250901071820","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Identifying potential biomarkers for the detection, diagnosis, and monitoring of cervical cancer (CC) constitutes a key area for future research.</p><p><strong>Methods: </strong>Differentially expressed genes (DEGs) and survival-associated DEGs (SDEGs) were identified using the GEPIA2 database through the TCGA-CESC dataset. The 3D structures of target proteins were predicted using trRosetta and validated via SAVES v6.0. Phytocompounds were retrieved from the PubChem database, and docking studies were performed using AutoDock Vina. The miRNAs regulating HK2 and MAP7 were also predicted by implementing miRNetv2.0 and the CancerMIRNome database. Finally, the anticancer activity of these compounds was validated individually and in combination using the ME180 and SiHa CC cell lines.</p><p><strong>Results: </strong>The present study identified the top five most hazardous novel biomarkers through DEGs (5763) and SDEGs (500) (P-value ≤ 0.05). The phytocompounds EGCG and myricetin interacted with HK2 with binding affinities of -8.3 and -8.1 kcal/mol and RMSDs of 1.369Å and 1.452Å, respectively. Similarly, EGCG (-9.1 kcal/mol) and myricetin (-7.9 kcal/mol), with the RMSD of 1.682Å and 1.148Å, showed strong bonding with the MAP7. EGCG and myricetin treatment synergistically inhibited ME180 (IC50 = 63.49μM) and SiHa (IC50 = 81.54μM) cell-proliferation. miRNAs regulating HK2 and MAP7 were identified, including hsa-mir-484 (HK2) and hsa-mir-17-5p, hsa-mir-93-5p, hsa-mir-106b-5p, among others (MAP7).</p><p><strong>Discussion: </strong>EGCG and myricetin, in combination, showed a synergistic effect on the ME180 cell line compared to the SiHa cell line.</p><p><strong>Conclusion: </strong>More in vitro and cell- and patient-derived xenograft models studies are needed to support the synergistic effect of EGCG and myricetin.</p>","PeriodicalId":10798,"journal":{"name":"Current gene therapy","volume":" ","pages":""},"PeriodicalIF":3.3000,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Synergistic Antiproliferative Effects of EGCG and Myricetin on Cervical Cancer Biomarkers in ME180 and SiHa Cell Lines.\",\"authors\":\"Kaviyaprabha Rangaraj, Miji Thandaserry Vasudevan, Suseela Rangaraj, Rachana Kumar, Sridhar Muthusami, Tahani Awad Alahmadi, Arunachalam Chinnathambi, Palanisamy Arulselvan, Chaiyavat Chaiyasut, Muruganantham Bharathi\",\"doi\":\"10.2174/0115665232363374250901071820\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Identifying potential biomarkers for the detection, diagnosis, and monitoring of cervical cancer (CC) constitutes a key area for future research.</p><p><strong>Methods: </strong>Differentially expressed genes (DEGs) and survival-associated DEGs (SDEGs) were identified using the GEPIA2 database through the TCGA-CESC dataset. The 3D structures of target proteins were predicted using trRosetta and validated via SAVES v6.0. Phytocompounds were retrieved from the PubChem database, and docking studies were performed using AutoDock Vina. The miRNAs regulating HK2 and MAP7 were also predicted by implementing miRNetv2.0 and the CancerMIRNome database. Finally, the anticancer activity of these compounds was validated individually and in combination using the ME180 and SiHa CC cell lines.</p><p><strong>Results: </strong>The present study identified the top five most hazardous novel biomarkers through DEGs (5763) and SDEGs (500) (P-value ≤ 0.05). The phytocompounds EGCG and myricetin interacted with HK2 with binding affinities of -8.3 and -8.1 kcal/mol and RMSDs of 1.369Å and 1.452Å, respectively. Similarly, EGCG (-9.1 kcal/mol) and myricetin (-7.9 kcal/mol), with the RMSD of 1.682Å and 1.148Å, showed strong bonding with the MAP7. EGCG and myricetin treatment synergistically inhibited ME180 (IC50 = 63.49μM) and SiHa (IC50 = 81.54μM) cell-proliferation. miRNAs regulating HK2 and MAP7 were identified, including hsa-mir-484 (HK2) and hsa-mir-17-5p, hsa-mir-93-5p, hsa-mir-106b-5p, among others (MAP7).</p><p><strong>Discussion: </strong>EGCG and myricetin, in combination, showed a synergistic effect on the ME180 cell line compared to the SiHa cell line.</p><p><strong>Conclusion: </strong>More in vitro and cell- and patient-derived xenograft models studies are needed to support the synergistic effect of EGCG and myricetin.</p>\",\"PeriodicalId\":10798,\"journal\":{\"name\":\"Current gene therapy\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2025-09-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Current gene therapy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2174/0115665232363374250901071820\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current gene therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2174/0115665232363374250901071820","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
Synergistic Antiproliferative Effects of EGCG and Myricetin on Cervical Cancer Biomarkers in ME180 and SiHa Cell Lines.
Introduction: Identifying potential biomarkers for the detection, diagnosis, and monitoring of cervical cancer (CC) constitutes a key area for future research.
Methods: Differentially expressed genes (DEGs) and survival-associated DEGs (SDEGs) were identified using the GEPIA2 database through the TCGA-CESC dataset. The 3D structures of target proteins were predicted using trRosetta and validated via SAVES v6.0. Phytocompounds were retrieved from the PubChem database, and docking studies were performed using AutoDock Vina. The miRNAs regulating HK2 and MAP7 were also predicted by implementing miRNetv2.0 and the CancerMIRNome database. Finally, the anticancer activity of these compounds was validated individually and in combination using the ME180 and SiHa CC cell lines.
Results: The present study identified the top five most hazardous novel biomarkers through DEGs (5763) and SDEGs (500) (P-value ≤ 0.05). The phytocompounds EGCG and myricetin interacted with HK2 with binding affinities of -8.3 and -8.1 kcal/mol and RMSDs of 1.369Å and 1.452Å, respectively. Similarly, EGCG (-9.1 kcal/mol) and myricetin (-7.9 kcal/mol), with the RMSD of 1.682Å and 1.148Å, showed strong bonding with the MAP7. EGCG and myricetin treatment synergistically inhibited ME180 (IC50 = 63.49μM) and SiHa (IC50 = 81.54μM) cell-proliferation. miRNAs regulating HK2 and MAP7 were identified, including hsa-mir-484 (HK2) and hsa-mir-17-5p, hsa-mir-93-5p, hsa-mir-106b-5p, among others (MAP7).
Discussion: EGCG and myricetin, in combination, showed a synergistic effect on the ME180 cell line compared to the SiHa cell line.
Conclusion: More in vitro and cell- and patient-derived xenograft models studies are needed to support the synergistic effect of EGCG and myricetin.
期刊介绍：
Current Gene Therapy is a bi-monthly peer-reviewed journal aimed at academic and industrial scientists with an interest in major topics concerning basic research and clinical applications of gene and cell therapy of diseases. Cell therapy manuscripts can also include application in diseases when cells have been genetically modified. Current Gene Therapy publishes full-length/mini reviews and original research on the latest developments in gene transfer and gene expression analysis, vector development, cellular genetic engineering, animal models and human clinical applications of gene and cell therapy for the treatment of diseases.
Current Gene Therapy publishes reviews and original research containing experimental data on gene and cell therapy. The journal also includes manuscripts on technological advances, ethical and regulatory considerations of gene and cell therapy. Reviews should provide the reader with a comprehensive assessment of any area of experimental biology applied to molecular medicine that is not only of significance within a particular field of gene therapy and cell therapy but also of interest to investigators in other fields. Authors are encouraged to provide their own assessment and vision for future advances. Reviews are also welcome on late breaking discoveries on which substantial literature has not yet been amassed. Such reviews provide a forum for sharply focused topics of recent experimental investigations in gene therapy primarily to make these results accessible to both clinical and basic researchers. Manuscripts containing experimental data should be original data, not previously published.
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