Pakistan Journal of Pharmaceutical Sciences

Abstract: Background: Cervical cancer continues to be a major cause of female cancer deaths globally, with dysregulation of the PTEN/PI3K/AKT pathway contributing to disease progression and treatment resistance. Baicalein, a bioactive flavonoid, exhibits anti-cancer properties through incompletely understood mechanisms. Objectives: To investigated whether baicalein promotes cervical cancer cell apoptosis by modulating PTEN expression and PI3K/AKT. Methods: In this study, we investigated the role of baicalein in promoting apoptosis in SiHa cervical cancer cells, with a focus on its potential modulation of PTEN expression and the PI3K/AKT pathway. Cell viability and apoptosis were assessed following baicalein treatment at various doses and time points. The expression levels of PTEN, PI3K, AKT, and Bcl-2 family proteins were analyzed to elucidate the molecular mechanisms. Additionally, the functional impact of PTEN overexpression, alone or in combination with baicalein, was evaluated. Results: We demonstrated that baicalein treatment (IC50 = 53.3 ?mol/L) induced dose- and time-dependent cytotoxicity and increased apoptosis through modulation of Bcl-2 family proteins. Mechanistically, baicalein upregulated PTEN expression while suppressing PI3K/AKT pathway components including AKT1 and PDK1. PTEN overexpression alone inhibited PI3K/AKT signaling and induced apoptosis (31.53%). Remarkably, combining baicalein with PTEN overexpression produced synergistic effects, achieving 46.83% apoptosis and maximally suppressing pro-survival signals while activating pro-apoptotic mechanisms. The combination treatment increased the Bax/Bcl-2 ratio 40-fold and reduced AKT1 and PDK1 expression by >80%. Conclusion: Our findings reveal that baicalein enhances PTEN tumor suppressor function to inhibit PI3K/AKT signaling, and suggest that combining natural compounds with tumor suppressor restoration represents a promising therapeutic strategy for cervical cancer.