Baicalein Exerts Cytotoxic Effects Through Cell Cycle Arrest and Mitochondria- Dependent Pathway in Ovarian Cancer Cells: In-Vitro and Computational Evaluation.
TL;DR
Findings showed that baicalein induces apoptosis in ovarian cancer PA-1 cells via a ROSmediated, mitochondria-dependent pathway and highlights the potential of baicalein as a promising lead compound for the development of anticancer therapeutics.
Abstract
INTRODUCTION Ovarian cancer remains one of the most prevalent and lethal gynecological malignancies globally, necessitating the exploration of novel therapeutic agents. Baicalein, a naturally occurring flavonoid, possesses potent antioxidant and anti-inflammatory properties and has recently gained attention for its anticancer potential. This study aimed to elucidate the anticancer efficacy and underlying molecular mechanisms of baicalein in human ovarian carcinoma PA-1 cells through comprehensive in vitro and in silico approaches.
Methods
PA-1 cells were exposed to increasing concentrations of baicalein, and cytotoxicity was assessed using the MTT assay. Apoptotic induction was evaluated by measuring mitochondrial membrane potential (MMP), reactive oxygen species (ROS) induction, and nuclear morphological changes using DAPI, Hoechst/PI, and AO/EB staining. Cell cycle checkpoints were analyzed by flow cytometry. Apoptosis-related genes (p53, Bax, Puma, Noxa, and Bcl-2) expression was quantified using qRT-PCR. In silico molecular docking was performed using PyRx to predict interactions with key apoptotic proteins, while SwissADME was employed to assess pharmacokinetic properties and drug-likeness.
Results
Baicalein significantly reduced PA-1 cell viability in a concentration-dependent manner and induced pronounced morphological changes characteristic of apoptosis. Treatment resulted in elevated ROS production, loss of MMP, nuclear condensation, and S-phase cell cycle arrest. Gene expression analysis demonstrated significant upregulation of pro-apoptotic markers (p53, Bax, Puma, and Noxa) alongside decreased expression of the anti-apoptotic gene Bcl-2. Molecular docking studies revealed favorable binding affinities of baicalein with apoptosis-regulating proteins, and SwissADME analysis confirmed acceptable drug-likeness and pharmacokinetic profiles.
Discussion
These findings showed that baicalein induces apoptosis in ovarian cancer PA-1 cells via a ROSmediated, mitochondria-dependent pathway.
Conclusion
This study highlights the potential of baicalein as a promising lead compound for the development of anticancer therapeutics.