Isolation of bioactive phytochemicals from Crinum asiaticum along with their cytotoxic and TRAIL-resistance abrogating prospect assessment

Crinum asiaticum L. (Amaryllidaceae) is a perennial bulbous herb, locally utilized for possessing multifaceted pharmacological properties including anticancer, immune-stimulating, analgesic, antiviral, antimalarial, antibacterial, and antifungal, in addition to their popularity as an aesthetic plant. Separation of MeOH extract of C. asiaticum leaves yielded three known compounds as cycloneolitsol ( 1 ), hippeastrine ( 2 ) and β-sitosterol ( 3 ). Among these, compounds 1 and 2 were subjected to the cytotoxic assay and found that 1 decreased cell viability to 45% and 8% against HCT116 cells; 15% and 9% against DU145 cells; 63% and 23% against Huh7 cells at 100 µM and 200 µM concentrations, respectively. Similarly, 2 decreased cell viability to 10% and 7% against HCT116 cells; 25% and 15% against DU145 cells; 26% and 18% against Huh7 cells at 100 µM and 200 µM concentrations, respectively. When tested for TRAIL-resistance abrogating activity, 1 (100 µM) along with TRAIL (100 ng/mL) showed moderate activity in AGS cells producing 25% more inhibition than the agent alone. Whereas (20 and 30 µM) in combination with TRAIL (100 ng/mL) exhibited strong activity in abrogating TRAIL-resistance and caused 34 and 36% more inhibition in AGS cells, respectively. The in-silico studies of compounds 1 and 2 revealed high docking hits in the TRAIL and other cancer-associated proteins which indicates a good correlation with the cell-based assay. It is still recommended to conduct further investigations to understand their exact molecular mechanism.