Sodium selenite promotes apoptosis and augments autophagic flux in cervical cancer cells by activating the YAP-Hippo signaling pathway

Background: Selenium (Se) compounds display selective cytotoxicity toward many tumors, yet their activity against cervical cancer is not well-established. This study evaluates the anti-cervical cancer effects of sodium selenite (SS) and clarifies the underlying mechanisms. Methods: HeLa cells were treated with graded SS concentrations. Cell viability was measured using the Cell Counting Kit-8, apoptosis was analyzed by Annexin V/PI flow cytometry, and cell migration and invasion were evaluated by scratch assay and Matrigel-Transwell assay, respectively. Autophagic activity and Hippo signaling were analyzed by Western blotting and immunofluorescence. For in vivo validation, 5-week-old female BALB/c nude mice bearing subcutaneous HeLa xenografts received SS (6 mg/kg intraperitoneally, every other day) or saline. Tumor volume was recorded, and excised tumor tissues underwent histopathology. Results: SS suppressed HeLa cell proliferation in a concentration- and time-dependent manner [24-h half-maximal inhibitory concentrations (IC50) ≈4.9 µM], heightened apoptosis, and markedly reduced migration and invasion. Molecular assays showed increased LC3-II accumulation with concomitant p62 degradation, indicating enhanced autophagic flux. These changes coincided with elevated phosphorylation of LATS1 and YAP and a reduction in total YAP, signifying Hippo signaling pathway activation, which was further confirmed by YAP knockdown-mediated inhibition of SS-induced autophagy. In xenograft models, SS slowed tumor growth and lowered proliferative and YAP immunostaining without overt toxicity. Conclusions: SS restrains cervical cancer progression by inducing apoptosis and accelerating autophagosome turnover through activation of the YAP-Hippo axis. These findings highlight SS and YAP-directed modulation in general, as promising avenues for future cervical cancer therapy development.