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Tumor Biology
Published in: Tumor Biology 3/2016

01-03-2016 | Original Article

Effects of silibinin on growth and invasive properties of human ovarian carcinoma cells through suppression of heregulin/HER3 pathway

Authors: Majid Momeny, Reza Ghasemi, Giovanni Valenti, Mariska Miranda, Ali Zekri, Ghazaleh Zarrinrad, Sepehr Javadikooshesh, Marjan Yaghmaie, Kamran Alimoghaddam, Ardeshir Ghavamzadeh, Seyed H. Ghaffari

Published in: Tumor Biology | Issue 3/2016

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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.
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Metadata
Title
Effects of silibinin on growth and invasive properties of human ovarian carcinoma cells through suppression of heregulin/HER3 pathway
Authors
Majid Momeny
Reza Ghasemi
Giovanni Valenti
Mariska Miranda
Ali Zekri
Ghazaleh Zarrinrad
Sepehr Javadikooshesh
Marjan Yaghmaie
Kamran Alimoghaddam
Ardeshir Ghavamzadeh
Seyed H. Ghaffari
Publication date
01-03-2016
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 3/2016
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-4220-6

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