Oleanolic acid inhibits cervical cancer Hela cell proliferation through modulation of the ACSL4 ferroptosis signaling pathway.

ABSTRACT

Cervical cancer remains the leading cause of cancerous death among women worldwide. Oleanolic acid (OA) is a substance that occurs naturally in the leaves, fruits, and rhizomes of plants and has anti-cancer activity. In this study, tumor-bearing mice were used as the animal model and Hela cells were used as cellular model. In vivo experiments have showed that OA significantly reduced the size and mass of cervical cancer tumors in mice. In vitro experiments have showed that OA significantly reduced the viability and proliferative capacity of Hela cells. In both in vivo and in vitro assays, OA increased the oxidative stress levels and Fe2+ content, and increased the expression of ferroptosis-related proteins. We found that ACSL4 was highly expressed in both xenograft models and cervical carcinoma cells with OA treatment. Further use of siRNA to interfere with ACSL4 expression in cervical cancer cells revealed that the inhibitory effect of OA on cell viability and proliferative capacity was counteracted, while a decrease in ROS levels and GPX4 was detected, suggesting that OA activated ferroptosis in Hela cells by promoting ACSL4 expression, thereby reducing the survival rate of Hela cells. Therefore, promotion of ACSL4-dependent ferroptosis by OA may be a potential approach for the treatment of cervical cancer.