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The inhibition of cordycepin on cancer stemness in TGF-beta induced chemo-resistant ovarian cancer cell

2017; Impact Journals LLC; Volume: 8; Issue: 67 Linguagem: Inglês

10.18632/oncotarget.22951

1949-2553

Chia-Woei Wang, Bao-Hong Lee, Chen‐Jei Tai,

Medicinal Plant Pharmacodynamics Research

// Chia-Woei Wang 1, 2 , Bao-Hong Lee 3, 4 and Chen-Jei Tai 1, 2, 3, 4 1 Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 11042, Taiwan 2 Department of Obstetrics and Gynecology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11042, Taiwan 3 Department of Traditional Chinese Medicine, Department of Internal Medicine, Taipei Medical University Hospital, Taipei 11042, Taiwan 4 Traditional Herbal Medicine Research Center, Taipei Medical University Hospital, Taipei 11042, Taiwan Correspondence to: Chen-Jei Tai, email: chenjtai@tmu.edu.tw Keywords: cancer stem cells; chemotherapy; chemoresistance; cordycepin; ovarian cancer Received: August 31, 2017 Accepted: November 15, 2017 Published: December 05, 2017 ABSTRACT Chemotherapy is one of the main approach for ovarian cancer. Cancer stem cells (CSCs) escape chemotherapy and lead to chemoresistance. We previously demonstrated that cordycepin (Cd) inhibited metastasis in human ovarian carcinoma cells, the aim of this study is to investigate the effects of Cd on ovarian cancer stemness. TGF-beta was used to induce chemoresistance of chemotherapeutic agent cisplatin in SKOV-3 ovarian cancer cells. After treating with 100 μM of Cd, cell viability, the percentage of cancer stem cells, and the levels of matrix metalloproteinases (MMPs) were decreased in TGF-beta-induced SKOV-3 cells. Treatment of Cd recovered E-cadherin levels and inhibited vimentin levels while TGF-beta treatment significantly increased the expression of vimentin and PGC-1alpha, and decreased E-cadherin levels in SKOV-3 cells, indicating that the action of Cd on cancer stemness may contribute to the regulation of epithelial-mesenchymal transition (EMT). Cd efficiently attenuated chemoresistance caused by TGF-beta in SKOV-3 cancer stem cells to promote the cytotoxicity of cisplatin.