A New Saponin (Zygo-albuside D) from Zygophyllum album Roots Triggers Apoptosis in Non-Small Cell Lung Carcinoma (A549 Cells) through CDK-2 Inhibition.

Phytochemical study of the ethyl acetate root extract of has resulted in the isolation of a new saponin, Zygo-albuside D (), along with two known compounds; (3-O-[β-D-quinovopyranosyl]-quinovic acid) (), which is first reported in the root, and catechin (), first reported in the genus. Their chemical structures were established by NMR and high-resolution mass spectrometry (HRMS). The new saponin () exhibited promising cytotoxicity with IC values of 3.5 and 5.52 μM on A549 and PC-3 cancer cell lines, respectively, compared to doxorubicin with IC values of 9.44 and 11.39 μM on A549 and PC-3 cancer cell lines, respectively. While it had an IC value of 46.8 μM against WISH cells. Investigating apoptosis-induction, compound induced total apoptotic cell death in A549 lung cancer cells by 32-fold; 21.53% compared to 0.67% in the untreated control cells. Finally, it upregulated the pro-apoptotic genes and downregulated the antiapoptotic gene using gene expression levels. Compound exhibited remarkable CDK-2 target inhibition by 96.2% with an IC value of 117.6 nM compared to Roscovitine. The molecular docking study further confirmed the binding affinity of compound as CDK2 and Bcl2 inhibitors that led to apoptosis induction in A549 cancer cells. Hence, this study highlights the importance of compound in the design of a new anticancer agent with specific mechanisms.