Multitarget Antiproliferative Activity of Pituranthos scoparius: An Integrated Phytochemical, Biological and Computational Insights into Key Oncogenic Pathways

Background: Pituranthos scoparius (Apiaceae), commonly known in Algeria as “Kozah”, is a medicinal plant traditionally used for various therapeutic purposes. However, its potential as a source of antiproliferative agents and its underlying molecular mechanisms remain poorly characterized. Purpose: This study aimed to investigate the antiproliferative potential of P. scoparius through an integrated strategy combining phytochemical profiling, in vitro evaluation, and computational approaches, with particular emphasis on its activity against key cancer-related pathways. Study Design: An integrated experimental–computational study was performed to explore the multitarget antiproliferative profile of P. scoparius extracts. Methods: Phytochemical characterization was carried out using LC-MS/MS and GC-MS/MS to identify the major bioactive constituents. Antiproliferative activity was assessed in vitro against human colorectal (HT-29) and hepatocellular carcinoma (HepG2) cell lines using the MTT assay. Molecular docking studies were conducted on selected major metabolites against relevant oncogenic targets, including PI3Kα, mTOR, COX-2, and BCL-2, to investigate potential mechanisms of action. Machine learning approaches were further employed to support the prediction of multitarget antiproliferative activity. Results: Chlorogenic acid and trans-ferulic acid were identified as the predominant phenolic compounds, while α-pinene was the major constituent of the essential oil. Both preparations exhibited significant dose- and time-dependent antiproliferative effects, with the essential oil showing enhanced cytotoxicity (IC50 up to 35.4 µg/mL). In silico analyses revealed strong binding affinities of key metabolites toward critical oncogenic proteins, particularly within the PI3Kα/mTOR signaling pathway. Machine learning predictions further supported a multitarget antiproliferative profile. Conclusions: P. scoparius represents a promising source of natural compounds with multitarget antiproliferative potential. The combined experimental and computational findings provide mechanistic insights into its activity and support its relevance within the context of natural product-based cancer therapy, highlighting its potential for further preclinical development.