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.

Misi He,Dongling Zou,Wen G Jiang,John Chester,Dong Wang,Jun Cai,Qi Zhou,Chen Wang,Bruno Lopes-Bastos

doi:10.18632/oncotarget.13413

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.

Highlights

Epithelial ovarian carcinomas (EOCs) accounts for nearly 90% of all malignant ovarian tumours and is the leading cause of death from gynaecologic malignant tumour [1]
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
EOCs are responsible for approximately 90% of all ovarian cancer cases and derived from ovarian surface epithelium stem cells or fallopian tube epithelium

Summary

Introduction

Epithelial ovarian carcinomas (EOCs) accounts for nearly 90% of all malignant ovarian tumours and is the leading cause of death from gynaecologic malignant tumour [1]. In contrast to most other solid tumours, the majority of EOC patients already are at the advanced stages (III or IV) disease when diagnosed. A current standard treatment for the patients with advanced ovarian cancer includes primary tumour cytoreductive surgery followed by cisplatinum-based chemotherapy since 1970. Cisplatin is administrated intravenously to cause DNA crosslink, leading to apoptosis of cancer cells. The current therapies for EOCs have dramatically been advanced recent years, approximately 85% of patients with EOCs will have recurrent disease within 2 years and become resistant to cisplatin. There is an urgent need to develop new therapeutic strategies for improving the efficacy of treatment of EOCs, including cisplatin

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Conclusion