FL118, a novel camptothecin analogue, suppressed migration and invasion of human breast cancer cells by inhibiting epithelial-mesenchymal transition via the Wnt/β-catenin signaling pathway.

Abstract

The aim of the current study was to investigate the effects of FL118, a novel camptothecin analogue, on migration and invasion of human breast cancer cells and the underlying mechanisms of those effects. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and a plate clone formation assay were used to examine inhibition of the proliferation of MDA-MB-231 cells by FL118. Cell cycle distribution was detected using flow cytometry. A wound healing assay and a transwell assay were performed to detect the effects of FL118 on migration and invasion of MDA-MB-231 cells, respectively. qRT-PCR, Western blotting, and immunocytochemistry were used to study the effects of FL118 on expression of epithelial-mesenchymal transition (EMT)-related molecules and Wnt/ β-catenin signaling components in MDA-MB-231 cells. The current results indicated that FL118 inhibited the proliferation, migration and invasion of MDA-MB-231 cells in a dose- and time-dependent manner. FL118 caused MDA-MB-231 cells to accumulate in the S phase. FL118 significantly suppressed the expression of vimentin while enhancing the expression of E-cadherin. Moreover, decreased expression of β-catenin and its targets survivin and cyclin Dl was detected in the nucleus of MDA-MB-231 cells. Taken together, the current results suggest that FL118 inhibited Wnt/β-catenin signaling, leading to suppressed EMT and decreased migration and invasion of breast cancer cells.

• Authors: Zhihong Yang, Lixia Ji, Guohui Jiang, Ranran Liu, Zhantao Liu, Yuecheng Yang, Qingxia Ma, Hongqin Zhao
• Journal: Bioscience trends (Biosci Trends) Vol. 12 Issue 1 Pg. 40-46 ( 2018) ISSN: 1881-7823 [Electronic] Japan
• PMID: 29553100 (Publication Type: Journal Article)

Chemical References

• 7-ethyl-7-hydroxy-10H-1,3-Dioxolo(4,5-g)pyrano(3',4':6,7)indolizino(1,2-b)quinoline-8,11(7H,12H)-dione
• BIRC5 protein, human
• Benzodioxoles
• Cadherins
• Cyclin D
• Indolizines
• Inhibitor of Apoptosis Proteins
• Survivin
• Vimentin
• beta Catenin
• Camptothecin

Topics

• Benzodioxoles (chemistry, pharmacology)
• Breast Neoplasms (pathology)
• Cadherins (metabolism)
• Camptothecin (analogs & derivatives, chemistry)
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Cyclin D (metabolism)
• Epithelial-Mesenchymal Transition (drug effects)
• Female
• Humans
• Indolizines (chemistry, pharmacology)
• Inhibitor of Apoptosis Proteins (metabolism)
• Neoplasm Invasiveness
• Survivin
• Vimentin (metabolism)
• Wnt Signaling Pathway (drug effects)
• beta Catenin (metabolism)