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

  • ACS Omega. 2023 Aug 8;8(33):30630-30639. doi: 10.1021/acsomega.3c04314.
Enas E Eltamany  1 ,  Mohamed S Nafie  2 ,  Dina M Hal  1 ,  Maged S Abdel-Kader  3  4 ,  Abdelghafar M Abu-Elsaoud  5  6 ,  Safwat A Ahmed  1 ,  Amany K Ibrahim  1 ,  Jihan M Badr  1 ,  Reda F A Abdelhameed  1  7
Affiliations
  • 1. Department of Pharmacognosy, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt.
  • 2. Department of Chemistry (Biochemistry program), Faculty of Science, Suez Canal University, Ismailia 41522, Egypt.
  • 3. Department of Pharmacognosy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia.
  • 4. Department of Pharmacognosy, Faculty of Pharmacy, Alexandria University, Alexandria 21215, Egypt.
  • 5. Department of Botany & Microbiology, Faculty of Science, Suez Canal University, Ismailia, Egypt.
  • 6. Department of Biology, College of Science, Imam Muhammad bin Saud Islamic University (IMSIU), Riyadh 11623, Saudi Arabia.
  • 7. Department of Pharmacognosy, Faculty of Pharmacy, Galala University, New Galala 43713, Egypt.
PMID: 37636931 DOI: 10.1021/acsomega.3c04314
Abstract

Phytochemical study of the ethyl acetate root extract of Zygophyllum album has resulted in the isolation of a new saponin, Zygo-albuside D (1), along with two known compounds; (3-O-[β-D-quinovopyranosyl]-quinovic acid) (2), which is first reported in the root, and catechin (3), first reported in the genus. Their chemical structures were established by NMR and high-resolution mass spectrometry (HRMS). The new saponin (1) exhibited promising cytotoxicity with IC50 values of 3.5 and 5.52 μM on A549 and PC-3 Cancer cell lines, respectively, compared to doxorubicin with IC50 values of 9.44 and 11.39 μM on A549 and PC-3 Cancer cell lines, respectively. While it had an IC50 value of 46.8 μM against WISH cells. Investigating apoptosis-induction, compound 1 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 1 exhibited remarkable CDK-2 target inhibition by 96.2% with an IC50 value of 117.6 nM compared to Roscovitine. The molecular docking study further confirmed the binding affinity of compound 1 as CDK2 and Bcl2 inhibitors that led to Apoptosis induction in A549 Cancer cells. Hence, this study highlights the importance of compound 1 in the design of a new Anticancer agent with specific mechanisms.

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