1. Repurposing homoharringtonine for thyroid cancer treatment through TIMP1/FAK/PI3K/AKT signaling pathway
- Author
-
Chuang Xi, Guoqiang Zhang, Nan Sun, Mengyue Liu, Nianting Ju, Chentian Shen, Hongjun Song, Quanyong Luo, and Zhongling Qiu
- Subjects
Phytopharmacy ,Molecular biology ,Cell biology ,Cancer ,Science - Abstract
Summary: Homoharringtonine (HHT), an alkaloid isolated from Cephalotaxus, is an effective anti-leukemia agent and exhibits inhibitory effects in various solid tumors. However, the impacts of HHT treatment on thyroid cancer (TC) remain unclear. Our findings demonstrated that HHT exhibited remarkable anti-TC activity that involved inhibiting cell proliferation, invasion, and migration, as well as inducing apoptosis. Proteomics analysis revealed that the expression of the tissue inhibitor of metalloproteinase 1 (TIMP1) was downregulated in TC cells after HHT treatment. TIMP1 overexpression promoted TC progression and partially reversed the anti-TC effects of HHT, while TIMP1 downregulation inhibited TC progression and enhanced the anti-TC effects of HHT. Furthermore, TIMP1 re-expression attenuated the enhancement of anti-TC effects of HHT induced by TIMP1 knockdown. Mechanistically, HHT exerted anti-TC effects by downregulating TIMP1 expression and then inactivating the FAK/PI3K/AKT signaling pathway. Taken together, our study demonstrated that HHT could inhibit TC progression by inhibiting the TIMP1/FAK/PI3K/AKT signaling pathway.
- Published
- 2024
- Full Text
- View/download PDF