Butein suppresses cervical cancer growth through the PI3K/AKT/mTOR pathway

Cervical cancer is the second most common women carcinoma worldwide and the fourth leading cause of cancer-associated mortality in women. Butein, a bioactive flavonoid isolated from numerous native plants, has been shown to induce apoptosis and inhibits migration and invasion in numerous human cancer cells. However, to the best of our knowledge, the effect of butein on human cervical cancer cells has not been reported. The present study aimed to determine the effect of butein on cell growth, apoptosis, migration and invasion and identify the associated molecular mechanism involved using HeLa human cervical cancer cells in vitro, and on tumor growth in a nude mouse model. It was found that butein notably inhibited cell viability, colony formation, migration and invasion, induced cell cycle at the G2/M stage and cell apoptosis, as well as enhanced caspase-3, -8 and -9 activity in HeLa cells in a dose-dependent manner. When administered intraperitoneally, butein inhibited the tumor growth of human cervical cancer xenograft tumors in the nude mouse model. Additionally, treatment with butein significantly increased reactive oxygen species (ROS) generation and reduced the phosphorylation of PI3K, AKT and mTOR expression, which contributes to the inhibition of the tumor growth of cervical cancer and reduction of oxidative stress. These findings suggested that butein serves as a potential therapeutic agent for the treatment of cervical cancer.