Lycorine, an isoquinoline alkaloid, inhibits breast cancer proliferation and metastasis involving cytoskeletal protein

Abstract

Background: Lycorine, an isoquinoline alkaloid, exhibits anti-breast cancer activity, but its mechanism of action remains unclear. Purpose: This work was conducted to investigate the mechanism of lycorine on breast cancer cell line MDA-MB-231 and MCF-7. Methods: Tandem Mass Tag (TMT) analysis identified differentially expressed proteins and the signal pathways after treatment with lycorine. Cytotoxicity of lycorine was assessed by MTT assay. Mitochondrial membrane potential and flow cytometry served to detect apoptosis and cell cycle. Colony formation and wound healing were measured by cell migration assay. Meanwhile, immunoblotting was performed to detect the target gene expression at protein. Moreover, the 4T1/Luc homograft tumor model investigated the effects of lycorine in vivo. Results: TMT results showed that 140 differentially expressed proteins were found after being treated with lycorine, mainly affecting Wnt/β-catenin signaling and tight junction. Lycorine significantly inhibited the proliferation of MDA-MB-231 and MCF-7 cells with IC50 values of 1.84 ± 0.21 μM and 7.76 ± 1.16 μM, respectively, blocked the cell cycle in the G2/M phase, induced a decrease in mitochondrial membrane potential. Further studies showed lycorine induced apoptosis in the breast cancer cells through regulating the expression of caspase-3, caspase-8, caspase-9, and PARP, it inhibited the breast cancer cell proliferation and metastasis via E-cadherin, β-catenin, and F-actin. Additionally, the in vivo assays demonstrated that lycorine suppresses the tumor growth of breast cancer. Conclusion: The above results indicate that lycorine affects the EMT via Wnt signaling and tight junction. It suggests the feasibility of lycorine as a potential anticancer drug candidate.