Micellar Curcumol for Maintenance Therapy of Ovarian Cancer by activating the FOXO3a

Abstract

Abstract Background: Maintenance therapy (MT) after postoperative platinum-based chemotherapy for ovarian cancer (OC) is crucial for delaying or preventing disease relapse. The current targeted drugs are only effective in about 30% of OC patients and the options for MT are limited. FOXO3a was considered as a potential target of chemotherapeutic drugs for OC due to its key role in inhibiting disease progression and recurrence. Curcumol, a major constituent of the plant Rhizoma Curcumae, is a low-toxic and effective anti-cancer drug which indicates that it is a potential candidate for MT. However, curcumol is indissolubility in water, with low bioavailability, and its pharmacological basis is unclear. Herein, Micellar curcumol (MC) was prepared for the therapy of OC. Parallel assessments of the anti-tumor ability and mechanism of MC were performed on two kinds of OC cells. Results: The results indicated that the IC50 of MC in two OC cells were as low as 37.69±2.43 and 28.54±1.58 μg/mL, respectively. Curcumol, by inhibiting phosphorylation at the AKTT308 site, activates the transcriptional activity of FOXO3a, which further promotes the recruitment of FOXO3a to the promoter sequence of endoplasmic reticulum stress-related PERK genes, inducing OC cells apoptosis. Moreover, the DiR-labeled MC could quickly accumulate in the tumor region within only 1h and maintain for 48 h in vivo. Further, MC inhibited the growth of SKOV3 cells on tumor-bearing nude mice by intravenous injection. Conclusions: Micellar loaded curcumol provides great feasibility to achieve efficient MT for OC based on the nanoplatforms of active ingredients from natural products.