Combretum quadrangulare Kurz extracts trigger apoptosis in HepG2 cells through modulation of survivin , Bcl‐2 and caspase‐3 genes

Background Combretum quadrangulare Kurz is a medicinal plant widely used in Asia. The leaf and seed extracts have been highlighted for possessing diverse biological activities, including cytotoxic effects against cancer cells. However, the underlying molecular mechanisms remain unclear. This study aimed to evaluate the cytotoxic effects of ethanol extracts from the leaves, roots, and seeds of C. quadrangulare Kurz on HepG2 liver cancer cells, with a focus on elucidating the mechanisms of apoptosis induction and associated gene expression changes. Results High‐performance liquid chromatography analysis revealed that the ethanol extracts of C. quadrangulare Kurz leaves (CLE), roots (CRE), and seeds (CSE) contained major phytochemical constituents, including phenolic acids, flavonoids, and terpenoids. After 72 h of treatment, CLE and CRE showed significantly higher cytotoxicity compared to CSE. Remarkably, CLE selectively targeted HepG2 cells over non‐cancerous cells. All three extracts effectively triggered apoptosis in HepG2 cells, as evidenced by Annexin V/PI staining. Molecular analyses revealed that the apoptosis was associated with decreased levels of the anti‐apoptotic genes Bcl‐2 and survivin, while caspase‐3 expression was markedly increased at both the transcriptional and translational levels. Notably, the expression levels of caspase‐8 and caspase‐9 remained unaffected, indicating that the apoptosis occurred independently of these initiator caspases. Conclusion The C. quadrangulare Kurz ethanol extracts demonstrated selective cytotoxicity against HepG2 cells by inducing apoptosis, characterized by the downregulation of survivin and Bcl‐2 and the upregulation of caspase‐3. These findings suggest that C. quadrangulare Kurz is a potential candidate for developing new anticancer therapies, warranting further investigation.