Elemene Nanoemulsion Inhibits Metastasis of Breast Cancer by ROS Scavenging

Abstract

Bo Han,1,* Tao Wang,1,* Zhigang Xue,2 Tao Wen,1 Ling Lu,3 Jie Meng,1 Jian Liu,1 Sizhu Wu,3 Jianchun Yu,2 Haiyan Xu1 1Department of Biomedical Engineering, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, People’s Republic of China; 2Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 3State Key Laboratory of Organic-Inorganic Composites, Beijing University of Chemical Technology, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Haiyan Xu; Jianchun Yu Email [email protected]; [email protected]: Elemene (C15H24) is a sesquiterpene compound extracted from the rhizome of Curcuma herbs. In the past decades, the anti-tumor activity of elemene has been observed in vitro and in some clinical practices. However, pharmacological mechanisms of elemene are not demonstrated adequately, which may lead to improper clinical applications. This study aimed to investigate the anti-tumor effect of elemene nanoemulsion in the mouse model of triple-negative breast cancer (TNBC) and reveal the underlying mechanisms.Methods: The ESR measurement and quantum mechanics simulation were used to characterize the antioxidant ability of elemene nanoemulsion. The murine breast cancer cell line 4T1 cells were inoculated subcutaneously into the left fourth mammary fat pad of BalB/c mice to establish a TNBC mice model. The H&E staining, immunohistochemical staining, DHE staining and Western blot were employed to evaluate the therapeutic effects of the elemene nanoemulsion on the TNBC mice.Results: It was shown that the elemene nanoemulsion prolonged the survival of the triple-negative breast cancer-bearing mice and inhibited the metastasis to lung and liver while did not induce significant cytotoxicity to the tumor cells. Mechanistic studies demonstrated that the elemene nanoemulsion effectively scavenged the reactive oxygen species (ROS) in vitro and in vivo, which decreased the stabilization of hypoxia-inducible factor-1α (HIF-1α) and consequently reduced angiogenesis in the tumor microenvironment as well as decreased the level of NLRP3 inflammasomes and IL-1β production. In addition, the elemene nanoemulsion downregulated the level of IL-1β in the RAW264.7 cells in exposure with LPS.Conclusion: In conclusion, due to the ROS scavenging ability, elemene nanoemulsion effectively inhibited the metastasis of the breast cancer cells to lung and liver and consequently prolonged the survival of TNBC mice.Keywords: elemene, breast cancer, ROS, macrophages, tumor microenvironment

Keywords

• elemene
• breast cancer
• ros
• macrophages
• tumor microenvironment