Re-purposing of curcumin as an anti-metastatic agent for the treatment of epithelial ovarian cancer: in vitro model using cancer stem cell enriched ovarian cancer spheroids
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Misi He1,2, Dong Wang2, Dongling Zou2, Chen Wang3, Bruno Lopes-Bastos1, Wen G Jiang1, John Chester4, Qi Zhou2, Jun Cai1
1Cardiff China Medical Research Collaborative, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK
2Department of Gynaecologic Oncology, Chongqing Cancer Institute, Chongqing, 400030, China
3Department of Orthopaedic surgery, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, 400021, China
4Institute of Cancer and Genetics, School of Medicine, Cardiff University, Cardiff, Cardiff CF14 4XN, UK
Qi Zhou, email: [email protected]
Jun Cai, email: [email protected]
Keywords: curcumin, spheroid formation, epithelial ovarian cancer (EOC), peritoneal metastasis, aldehyde dehydrogenase 1 family member A1 (ALDH1A1)
Received: August 04, 2016 Accepted: November 08, 2016 Published: November 16, 2016
Malignant epithelial ovarian cancer (EOC) spheroids high frequently are detected in the malignant ascites of the patients with the extensive peritoneal metastasis of ovarian cancer, which represent a significant obstacle to efficacious treatment. Clinical data also suggested that EOC spheroids play a putative role in the development of chemoresistance. Since standard surgery and conventional chemotherapy is the only available treatment, there is an urgent need to identify a more effective therapeutic strategy. Recent studies demonstrated that curcumin exerts an anticancer effect in a variety of human cancers including ovarian cancer. This study evaluates anti-peritoneal metastasis and chemoresistance of curcumin related to the EOC spheroids. In this study, we confirm that the high invasive EOC cells forming the spheroids express a high level of a cancer stem cell (CSC) marker, aldehyde dehydrogenase 1 family member A1 (ALDH1A1), which was significantly down-regulated by curcumin treatment. Curcumin treatment markedly enhances the sensitivity of EOC spheroids to cisplatin in a dose-dependent manner. Our experiments provided evidence that curcumin could abolish the sphere-forming capacity of EOC cells in a dose-dependent manner. Moreover, curcumin substantially suppressed the growth of the pre-existed EOC spheroids, inhibited the adhesion of EOC spheroids to ECM as well as the invasion of EOC spheroids to the mesothelial monolayers. We propose to re-purpose curcumin as anti-metastatic and chemoresistant agent for EOC management in combination with conventional regimen. Further preclinical studies are necessary to validate the anti-cancer effect of curcumin in patients with EOC.
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