Mesua ferrea L. extract inhibits cell invasion and tumor growth in breast cancer in vitro and in vivo

Mesua ferrea L. was commonly used in Uyghur medicine, and the flowering buds of M. ferrea extract exhibited significant inhibitory effects on the proliferation of breast cancer cells in our preliminary research; however, the underlying active components remain to be elucidated. In this study, firstly, we extracted the flowering buds of M. ferrea with methanol and obtained eleven bioactive sub-fractions (MF-P-1-MF-P-11), and MF-P-5 showed the strongest inhibitory activity against MDA-MB-231 and 4T1 cells. Subsequently, 52 compounds from MF-P-5 were identified by UPLC Q-TOF MS/MS. In addition, ten compounds (MF1-MF10) from MF-P-5 were separated and identified, and MF5 could inhibit MDA-MB-231 and 4T1 cells proliferation as MTT and colony formation assay, suppress the migration of MDA-MB-231 and 4T1 cells by means of wound healing assay, reduce the expression level of E-cadherin, and induce MDA-MB-231 and 4T1 cells apoptosis by Annexin V-FITC/PI double staining assay and up-regulate the expression of Bax and down-regulate the expression of PARP. Ultimately, we evaluated the effects of MF-P-5 on breast cancer via MDA-MB-231 cell xenograft in nude mice. The results of tumor volume and weight and immunohistochemistry revealed that MF-P-5 could significantly inhibit the growth of MDA-MB-231 cells in vivo. Besides, the expression levels of E-cadherin significantly increased and MMP-2 decreased. The above results suggested that MF-P-5 could suppress the invasion of breast cancer cells in vivo. Furthermore, the expression level of Bcl-2 was prominently reduced which revealed that MF-P-5 stimulated the mitochondrial apoptosis pathway in vivo. As a result, MF5 could inhibit MDA-MB-231 and 4T1 cells proliferation, migration and tumor growth in vitro and MF-P-5 could suppress tumor growth in vivo which had laid a theoretical foundation for further clinical application.