title: 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.
abstract: 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.
authors.affiliation: Cardiff China Medical Research Collaborative, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK.|Department of Gynaecologic Oncology, Chongqing Cancer Institute, Chongqing, 400030, China.
authors.forename: Misi
authors.initials: M
authors.lastname: He
authors.affiliation: Department of Gynaecologic Oncology, Chongqing Cancer Institute, Chongqing, 400030, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Gynaecologic Oncology, Chongqing Cancer Institute, Chongqing, 400030, China.
authors.forename: Dongling
authors.initials: D
authors.lastname: Zou
authors.affiliation: Department of Orthopaedic surgery, Chongqing Hospital of Traditional Chinese Medicine, Chongqing, 400021, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.affiliation: Cardiff China Medical Research Collaborative, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK.
authors.forename: Bruno
authors.initials: B
authors.lastname: Lopes-Bastos
authors.affiliation: Cardiff China Medical Research Collaborative, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK.
authors.forename: Wen G
authors.initials: WG
authors.lastname: Jiang
authors.affiliation: Institute of Cancer and Genetics, School of Medicine, Cardiff University, Cardiff, Cardiff CF14 4XN, UK.
authors.forename: John
authors.initials: J
authors.lastname: Chester
authors.affiliation: Department of Gynaecologic Oncology, Chongqing Cancer Institute, Chongqing, 400030, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Cardiff China Medical Research Collaborative, School of Medicine, Cardiff University, Cardiff CF14 4XN, UK.
authors.forename: Jun
authors.initials: J
authors.lastname: Cai
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000032:analysis; D000080924:Aldehyde Dehydrogenase 1 Family; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000077216:Carcinoma, Ovarian Epithelial; D003474:Curcumin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy* / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010534:Peritoneal Neoplasms / Q000556:secondary*; D050697:Retinal Dehydrogenase; D018874:Spheroids, Cellular
chemical_list: D000970:Antineoplastic Agents; D000080924:Aldehyde Dehydrogenase 1 Family; D000444:Aldehyde Dehydrogenase; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase; D003474:Curcumin
keywords: aldehyde dehydrogenase 1 family member A1 (ALDH1A1); curcumin; epithelial ovarian cancer (EOC); peritoneal metastasis; spheroid formation