Malignant biological behaviors of triple-negative breast cancer cells mitigated by daphnetin through suppression of the PI3K-AKT-mTOR signaling cascade and activation of autophagy.

Breast cancer and triple-negative breast cancer (TNBC) are the most prevalent and malignant forms of tumors in women worldwide. Herein, daphnetin inhibited the proliferation, migration, and invasion of MDA-MB-231 triple-negative breast cancer cells in a dose-dependent process and also inhibited apoptosis. At the molecular level, daphnetin decreased the expression of PCNA, MMP-2, MMP-9, Ki67 and Bcl-2 and increased the expression of Bax. Moreover, daphnetin increased autophagic activity, which was supported by the decrease in the autophagy marker protein p62 and the increase in autolysosome formation. The PI3K-AKT-mTOR signaling cascade can be inhibited by daphnetin, preventing cancer progression. The current results indicate that the oncogenic behavior of MDA-MB-231 TNBC cells is suppressed by daphnetin, which involves both downregulation of the PI3K-AKT-mTOR signaling cascade and subsequent activation of autophagy.