Isoharringtonine inhibits breast cancer stem-like properties and STAT3 signaling

Abstract

Objectives: Breast cancer stem cells (BCSCs) contribute to breast cancer progression, relapse, and treatment resistance. Identification of the natural inhibitory components of BCSCs is therefore critical for clinical treatment. Here, we investigated whether isoharringtonine (IHT) had inhibitory effects on BCSCs in breast cancer cell lines.

Methods: HCC1806, HCC1937, and MCF7 cells were treated with IHT. The proliferation and the migration of cells were detected by MTS assay and wound healing migration assay, respectively. The proportions of BCSCs were determined by flow cytometry and tumor sphere formation assay. Using real-time quantitative polymerase chain reaction (qRT-PCR) and Western blotting, the expression of Nanog and activation of STAT3 were detected, respectively.

Results: Results showed that IHT inhibited the proliferation of HCC1806, HCC1937, and MCF-7 cells, and suppressed the migration of HCC1806 and HCC1937 cells in a dose-dependent manner. IHT treatment decreased the proportion of BCSCs in MCF-7, HCC1806, and HCC1937 cells. In addition, the mRNA level of Nanong was significantly downregulated after IHT treatment. We also found an inhibitory effect of IHT on STAT3 activation.

Conclusion: IHT inhibited the proliferation, migration, and BCSC proportion of breast cancer cell lines via inhibition of the STAT3/Nanong pathway.

Keywords: Cancer stem cells; Isoharringtonine; STAT3; Triple-negative breast cancer.