Tehran University of Medical Sciences

Science Communicator Platform

Stay connected! Follow us on X network (Twitter):
Share this content! On (X network) By
Effects of Silibinin on Growth and Invasive Properties of Human Ovarian Carcinoma Cells Through Suppression of Heregulin/Her3 Pathway Publisher Pubmed



Momeny M1 ; Ghasemi R2 ; Valenti G3 ; Miranda M4 ; Zekri A5 ; Zarrinrad G1 ; Javadikooshesh S1, 5 ; Yaghmaie M1 ; Alimoghaddam K1 ; Ghavamzadeh A1 ; Ghaffari SH1
Authors
Show Affiliations
Authors Affiliations
  1. 1. Hematology/Oncology and Stem Cell Transplantation Research Center, Shariati Hospital, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Department of Surgery, Division of Cardiothoracic Surgery, Washington University in St. Louis, Saint Louis, MO, United States
  3. 3. Department of Cancer Research, Max Delbrueck Center for Molecular Medicine, Berlin, Germany
  4. 4. QIMR Berghofer Medical Research Institute, Queensland, Australia
  5. 5. Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

Source: Tumor Biology Published:2016


Abstract

Epithelial ovarian cancer (EOC) is the most fatal gynecological malignancy due to its high proliferative and invasive capacities. A heregulin (HRG)/HER3 autocrine loop increases proliferative and metastatic properties of EOC cells, suggesting that modulators of this signaling pathway may prove effective to trammel growth and motility of these cells. This study aimed to evaluate the effects of multi-tyrosine kinase inhibitor silibinin on proliferative and invasive characteristics of EOC cell lines OVCAR8 and SKOV3 through suppression of the HRG/HER3 pathway. To achieve this, the effects of silibinin on proliferation, DNA synthesis, clonogenicity, cell cycle progression, cathepsin B enzymatic activity, and migration and invasion were explored in vitro. Silibinin suppressed proliferation, DNA synthesis, and clonogenic abilities of OVCAR8 and SKOV3 cells through inhibition of the autocrine HRG/HER3 circuit. Silibinin-mediated attenuation of the HER3 signaling disabled the HER3/AKT/survivin axis and thereby, induced G1/S cell cycle arrest. Furthermore, silibinin reduced invasive potentials of the EOC cells through quelling the HRG/HER3 pathway and suppression of cathepsin B activity. Altogether, these results suggest that silibinin is a potential anti-cancer drug to inhibit proliferative and invasive characteristics of the EOC cells that exhibit an autocrine HRG/HER3 pathway. © 2015, International Society of Oncology and BioMarkers (ISOBM).
Related Docs
View other Related Docs
1. Dacomitinib, a Pan-Inhibitor of Erbb Receptors, Suppresses Growth and Invasive Capacity of Chemoresistant Ovarian Carcinoma Cells, Scientific Reports (2017)
2. Blockade of Vascular Endothelial Growth Factor Receptors by Tivozanib Has Potential Anti-Tumour Effects on Human Glioblastoma Cells, Scientific Reports (2017)
3. Her2 Overexpression in Borderline and Malignant Ovarian Tumors: A Cross-Sectional Study in an Iranian Population and Literature Review, Middle East Journal of Cancer (2018)
4. A Novel Tumor Inhibitory Hybridoma Monoclonal Antibody With Dual Specificity for Her3 and Her2, Current Research in Translational Medicine (2021)
5. Inhibitory Effect of Polyclonal Antibodies Against Her3 Extracellular Subdomains on Breast Cancer Cell Lines, Asian Pacific Journal of Cancer Prevention (2020)
6. Blockade of Nuclear Factor-Κb (Nf-Κb) Pathway Inhibits Growth and Induces Apoptosis in Chemoresistant Ovarian Carcinoma Cells, International Journal of Biochemistry and Cell Biology (2018)
7. Overview of Cd24 As a New Molecular Marker in Ovarian Cancer, Journal of Cellular Physiology (2019)
8. Multiple Functions of P27 in Cell Cycle, Apoptosis, Epigenetic Modification and Transcriptional Regulation for the Control of Cell Growth: A Double-Edged Sword Protein, DNA Repair (2018)
Experts (# of related papers)
View all Related Experts
Seyed Hamidollah Ghaffari (8)
Ahmad Reza Dehpour (7)
Other Related Docs
9. Production of Human Single-Chain Fragment Antibody (Scfv) Against Human Epidermal Growth Factor Receptor-2 (Her-2) by Phage Display Technology, In Vitro Cellular and Developmental Biology - Animal (2018)
10. Anti-Tumour Activity of Tivozanib, a Pan-Inhibitor of Vegf Receptors, in Therapy-Resistant Ovarian Carcinoma Cells, Scientific Reports (2017)
11. The Erbb Receptor Inhibitor Dacomitinib Suppresses Proliferation and Invasion of Pancreatic Ductal Adenocarcinoma Cells, Cellular Oncology (2019)
12. Differential Tumor Inhibitory Effects Induced by Her3 Extracellular Subdomain-Specific Mouse Monoclonal Antibodies, Cancer Chemotherapy and Pharmacology (2022)
13. Inhibition of Bromodomain and Extraterminal Domain Reduces Growth and Invasive Characteristics of Chemoresistant Ovarian Carcinoma Cells, Anti-Cancer Drugs (2018)
14. An In-Silico Approach to Find a Peptidomimetic Targeting Extracellular Domain of Her3 From a Her3 Nanobody, Computational Biology and Chemistry (2017)
15. New Aspects of Silibinin Stereoisomers and Their 3-O-Galloyl Derivatives on Cytotoxicity and Ceramide Metabolism in Hep G2 Hepatocarcinoma Cell Line, Iranian Journal of Pharmaceutical Research (2016)
16. Anti-Tumor Activity of Cediranib, a Pan-Vascular Endothelial Growth Factor Receptor Inhibitor, in Pancreatic Ductal Adenocarcinoma Cells, Cellular Oncology (2020)
17. Cediranib, an Inhibitor of Vascular Endothelial Growth Factor Receptor Kinases, Inhibits Proliferation and Invasion of Prostate Adenocarcinoma Cells, European Journal of Pharmacology (2020)