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.

Differential Inhibitory Effects of Curcumin Between HPV+ve and HPV–ve Oral Cancer Stem Cells

“…It is further shown that curcumin causes loss of proliferation of oral cancer and CSCs. Our findings are consistent with previous studies on breast ( 22 ), colon ( 9 ), cervical ( 11 ), and ovarian cancer ( 23 ). Curcumin treatment inhibited cell viability more effectively in HPV+ve and HPV–ve parental and NSP than that of CSCs.…”

“…Less cytotoxic effect on CSCs could be attributed to limited penetration or inadequate availability of curcumin to SP cells. Similar results were also observed in earlier studies ( 23 , 24 ). However, inhibition of proliferation was found to be highly pronounced in HPV+ve CSCs than that of HPV–ve CSCs.…”

NOX4-mediated ROS production induces apoptotic cell death via down-regulation of c-FLIP and Mcl-1 expression in combined treatment with thioridazine and curcumin

“…Curcumin could induce apoptosis in cancer cells [19] , [20] , [21] , [22] , [23] , [24] as well as inhibit VEGF and osteopontin-induced angiogenesis [25] , [26] . Furthermore, curcumin inhibits H 2 O 2 -induced invasion of pancreatic cancer [27] and blocks invasion of ovarian cancer spheroids into the mesothelial monolayers [28] . In addition, many groups have reported that curcumin enhances TRAIL-, 5-fluorouracil-, gemcitabine- and irradiation-induced cell death [29] , [30] , [31] , [32] , [33] , [34] , [35] .…”

Synthesis and Properties of CurNQ for the Theranostic Application in Ovarian Cancer Intervention

“…Epithelial ovarian carcinoma (OC) is the most common type of OC, accounting for 90% of ovarian tumors. Symptoms of OC are detected late resulting in diagnosis at stages III and IV [ 10 , 11 ]. In addition, the highly metastatic nature of OC results in low patient survival with a mortality of approximately 60% [ 12 ].…”