Dual opposing effects of TBBPS/TCBPA on cervical cell proliferation: suppression in normal cells versus promotion in cancer via the cGAS-STING pathway

TBBPS and TCBPA are increasingly used as alternatives to tetrabromobisphenol A (TBBPA) and have been detected in various environmental samples. Moreover, they have been widely detected in human biological matrices such as blood, milk, <i>et al</i>. In view of this, it is particularly urgent to comprehensively evaluate the toxicological properties of TBBPS/TCBPA. In this study, in vitro experiments were carried out with cervical cancer cell models and normal cervical cell models. Comprehensive biochemical experiments were conducted to examine the effects of TBBPS and TCBPA on cervical cancer cells. Cell proliferation assays with CCK8 and EdU demonstrated that TBBPS and TCBPA enhance cervical cancer cell proliferation and enhance the expression of proliferation-related molecules. Subsequent research demonstrated that TBBPS/TCBPA enhance the secretion of inflammatory factors in cervical cancer cells, influencing cell proliferation. In the cervical epithelial cell model, our study revealed that TBBPS/TCBPA suppressed the proliferation of normal cervical epithelial cells. Mechanistic studies revealed that TBBPS/TCBPA treatment enhanced ds-DNA release, thereby activating the cGAS-STING signaling pathway and inhibiting cell proliferation. This study concludes that TBBPS/TCBPA exhibit dual effects by promoting cervical cancer cell growth while inhibiting normal cervical cell proliferation, which was mediated through the regulation of the inflammatory response. This study's findings will serve as a foundation for evaluating the potential health risks posed by TCBPA/TBBPS exposure.