Micellar curcumol for maintenance therapy of ovarian cancer by activating the FOXO3a

• Published in: Nanomedicine 2024-11, Vol.62, p.102789, Article 102789
• Main Authors: Wang, Jing, Chen, Bing, Yang, Jiezhen, Tang, Qin, Zhong, Yan, Du, Jiyu, Wang, Sheng, Wu, Qiang, Lu, Yang, Song, Yonghong
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; Curcumol; Female; Forkhead Box Protein O3 - metabolism; FOXO3a; Humans; Mice; Mice, Inbred BALB C; Mice, Nude; Micelle; Micelles; Ovarian cancer; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - metabolism; Ovarian Neoplasms - pathology; Sesquiterpenes - chemistry; Sesquiterpenes - pharmacology; Sesquiterpenes - therapeutic use; Therapy; Xenograft Model Antitumor Assays
• ISSN: 1549-9634; 1549-9642; 1549-9642
• DOI: 10.1016/j.nano.2024.102789

Maintenance therapy (MT) for ovarian cancer (OC) is crucial for preventing disease relapse. Curcumol shows effective anti-OC ability and low-toxicity to the normal ovarian epithelial cells, however, its bioavailability is low. Herein, micellar loaded curcumol (MC) was prepared and the anti-tumor ability of MC were performed on OC cells. The results indicated that the IC50 values of MC in two kinds of OC cells were 37.69 ± 2.43 and 28.54 ± 1.58 μg/mL, respectively. Mechanistically, curcumol could interact with the AKTThr308 site, inhibiting the phosphorylation of FOXO3a, which promoted FOXO3a nuclear locating and recruited it to the PERK promoter, activating the ERS induced apoptosis pathway. Moreover, MC inhibited the growth of SKOV3 cells on tumor-bearing nude mice and the DiR-labeled MC could quickly accumulate in the tumor region. MC provides great feasibility to achieve efficient MT for OC based on the nanoplatforms of active ingredients from natural products. Schematic of micellar curcumol (MC) and MC could accumulate in ovarian cancer (OC) tumor region rapidly after injected into mice intravenously. Mechanistically, curcumol interacted with the AKTThr308 site, inhibiting FOXO3a phosphorylation, which promoted FOXO3a nuclear locating, and recruited the FOXO3a to the PERK promotor to activate the ERS-induced apoptosis pathway in OC cells. [Display omitted]