Abstract
Formononetin, a phytoestrogen extracted from various herbal plants, has been investigated as an anticancer agent against diverse types of cancer. The aim of the present study was to investigate the induction of apoptotic cell death by formononetin in the FaDu pharyngeal squamous cell carcinoma cell line. Formononetin significantly increased FaDu cell death, with an estimated IC50 value of 50 µM; however, it did not affect the viability of normal L929 mouse fibroblasts used as normal control at 5‑25 µM. Typical characteristics of apoptosis, such as morphological alterations, chromatin condensation, DNA fragmentation and the size of the apoptotic cell population, were increased in FaDu cells treated with formononetin for 24 h. Furthermore, formononetin‑induced FaDu cell death involved the death receptor‑mediated extrinsic and the mitochondria‑dependent intrinsic apoptotic pathways by activating the caspase cascade. The chemotherapeutic effects of formononetin were mediated by the suppression of mitogen‑activated protein kinases, including extracellular signal‑regulated kinase 1/2 and p38, and nuclear factor‑κB phosphorylation in FaDu cells. Finally, the oral administration of formononetin decelerated tumor growth through the expression of cleaved caspase‑3 in a FaDu cell xenograft animal model. Taken together, these findings indicate that formononetin holds promise as a chemotherapeutic agent and may be of value in the treatment of human head and neck squamous cell carcinoma.