Silibinin exerts anti-cancer activity on human ovarian cancer cells by increasing apoptosis and inhibiting epithelial-mesenchymal transition (EMT)

• Published in: Gene 2022-05, Vol.823, p.146275-146275, Article 146275
• Main Authors: Maleki, Narges, Yavari, Negar, Ebrahimi, Maryam, Faisal Faiz, Ahmad, Khosh Ravesh, Roya, Sharbati, Aysan, Panji, Mohammad, Lorian, Keivan, Gravand, Abdollah, Abbasi, Mojtaba, Abazari, Omid, Shafiee Mehr, Mehdi, Eskandari, Yasin
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents, Phytogenic - administration & dosage; Antineoplastic Agents, Phytogenic - pharmacology; Apoptosis; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Cell Line, Tumor; Cell Movement - drug effects; Cell Proliferation - drug effects; Cell Survival - drug effects; Epithelial-mesenchymal transition; Epithelial-Mesenchymal Transition - drug effects; Female; Gene Expression Regulation, Neoplastic - drug effects; Humans; Invasion; Mice; Neoplasm Invasiveness; Ovarian cancer; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - genetics; Ovarian Neoplasms - metabolism; Silibinin; Silybin - administration & dosage; Silybin - pharmacology; Xenograft Model Antitumor Assays
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/j.gene.2022.146275

[Display omitted] •EMT is considered as a hallmark of cancer.•Silibinin inhibits EMT-related markers in ovarian cancer cells. Silibinin, the principal flavonoid derived from milk thistle seeds, has been demonstrated to have strong inhibitory effects against human malignancies. The inhibitory function of silibinin on ovarian cancer, however, is not fully identified. In this essay, both in vivo and in vitro investigations were conducted to survey the silibinin's blocking effects on ovarian cancer. The impacts of silibinin on two ovarian cancer cell lines, SKOV-3 and A2870, were determined by evaluating cell viability, migration, invasion, and apoptosis. Q-RT-PCR and western blotting techniques were carried out to explore the protein levels of signaling pathway markers. A mouse xenograft model was utilized to determine the silibinin efficacy in inhibiting tumor growth. After cell treatment with silibinin, cell viability, migration, and invasion were appreciably inhibited in cancer cell lines, but cell apoptosis was promoted. Also, silibinin reversed the epithelial-mesenchymal transition (EMT) mechanism by inducing E-cadherin expression and reducing N-cadherin and vimentin expression, suppressing the levels of regulators related to EMT such as Snail, Slug, and ZEB1 transcription factors, and also decreasing PI3K/AKT, Smad2/3, and β-catenin intermediate molecules in vitro. Silibinin effectively ameliorated tumor growth in vivo. silibinin could be considered a potent agent against ovarian cancer based on the results.