Antiproliferative and Anti-Metastatic effects of ethanolic Leaf Extract of Cascabela Thevetia against Cholangiocarcinoma Cells

Abstract

Cascabela thevetia (syn. Thevetia peruviana) is a medicinally important flowering plant traditionally used for the treatment of wounds, skin infections, tumours, and other ailments. With the increasing incidence of multidrug-resistant (MDR) bacterial infections and aggressive cancers such as cholangiocarcinoma, the present study aimed to evaluate the phytochemical composition, antibacterial activity, and anticancer potential of C. thevetia leaf and flower extracts. Ethanolic and aqueous extracts of leaves (CtLEt, CtLAq) and flowers (CtFEt, CtFAq) were prepared by successive extraction. Phytochemical analysis revealed variation among extracts, with CtLAq showing higher amino acid, phenolic, and metal-reducing content, while CtLEt exhibited higher protein and flavonoid levels. Qualitative screening confirmed the presence of tannins and glycosides in ethanolic extracts and saponins, terpenoids, and phlobatannins in aqueous extracts. All extracts demonstrated low hemolytic toxicity (<10% RBC lysis). Antibacterial evaluation against MDR Enterococcus faecalis and Shigella spp. revealed that CtLEt exhibited the strongest activity against both strains with a minimum inhibitory concentration (MIC) of 10 mg/ml. CtLAq and CtFEt showed selective antibacterial effects, whereas CtFAq showed no activity. Importantly, CtLEt demonstrated significant anticancer potential against cholangiocarcinoma cell lines by reducing cell viability and proliferation, inhibiting cell migration, and suppressing colony formation. These findings suggest that C. thevetia, particularly the ethanolic leaf extract, possesses promising antibacterial and multifaceted anticancer properties, highlighting its potential as a source of novel therapeutic agents against MDR infections and cholangiocarcinoma.