Tanshinone I Promotes Ferroptosis of Cervical Cancer Cells by Activating the ATF3-Mediated Transcriptional Inhibition of FSP1.

Cervical cancer (CC) remains a significant global health concern for women, highlighting the urgent need for effective therapeutic strategies. In recent years, natural active compounds derived from traditional Chinese medicine have garnered increasing attention for their antitumor potential. Tanshinone I (Tan I) is a tanshinone compound with extensive anticancer activity extracted from the Chinese herb Danshen. However, Tan I has been poorly studied for its use in CC. This study explored the antitumour mechanism of Tan I in CC both in vitro and in vivo. In vitro experiments revealed that Tan I inhibited the proliferation, migration and invasion of HeLa and CaSki cells via the induction of ferroptosis. We also found that Tan I induced the expression of activating transcription factor 3 (ATF3), which is closely related to ferroptosis, through ER stress. Further knockdown of ATF3 in HeLa and CaSki cells revealed that the suppressive effects of Tan I on cellular functions were offset. In vivo experiments revealed that Tan I promoted ferroptosis in CC cells and inhibited tumour growth by inducing ATF3 expression. Mechanistically, both cell and subcutaneous xenograft mouse model experiments demonstrated that Tan I promoted ferroptosis and inhibited the malignant progression of CC by regulating the ATF3‒FSP1 axis. In conclusion, this study explored the antitumour mechanism of Tan I in CC, and the results indicated that Tan I may be a potentially effective drug for CC treatment, which may be beneficial for the development of less toxic and more effective therapeutic agents.